Reduction of trans-dichloro- and trans-dibromo-tetracyanoplatinate(IV) by L-methionine

Reduction of trans-[Pt(CN) 4 X 2 ] 2- (X = Cl or Br) [as model compounds for antitumour-active platinum(IV) pro-drugs] to [Pt(CN) 4 ] 2- by L-methionine, MeSR, has been studied at 25 °C in the range 0 < pH < 12 (X = Cl) and 0 < pH < 6 (X = Br) by use of stopped-flow spectrophotometry. The stoichiometry is [Pt IV ]:[MeSR] ≈ 1: 1; the reaction products are methionine S-oxide and [Pt(CN) 4 ] 2- as identified by NMR and UV spectroscopies, respectively. The kinetics is first order with respect to the platinum(IV) and methionine concentrations and the second-order rate constants have a small pH dependence. In analogy with reduction of platinum(IV) complexes by thioglycolic acid, cysteine, penicillamine and glutathione, a mechanism is postulated in which [Pt(CN) 4 X 2 ] 2- is reduced by the various protolytic species of methionine in parallel reactions. In the transition state the thioether group of methionine is assumed to interact with co-ordinated halide, mediating the electron transfer to the platinum(IV) centre. The transition states for previously studied reactions between [Pt(CN) 4 X 2 ] 2- and thiols are discussed in view of these results. It is concluded that methionine-containing biomolecules may compete with thiol compounds for reduction of platinum(IV) pro-drugs under acidic conditions, and also in neutral solutions with low concentrations of thiol-containing biomolecules.