REDUCTION OF TRANS-DICHLORO-PLATINATE(IV) AND TRANS-DIBROMO-TETRACYANO-PLATINATE(IV) BY L-METHIONINE

Reduction of trans-[Pt(CN)(4)X-2](2-) (X = Cl or Br) [as model compoun ds for antitumour-active platinum(iv)pro-drugs] to [Pt(CN)(4)](2-) by L-methionine, MeSR, has been studied at 25 degrees C in the range 0 < pH < 12(X = Cl) and 0 < pH < 6 (X = Br) by use of stopped-flow spectro photometry. The stoichiometry is [Pt-IV]:[MeSR]approximate to 1:1; the reaction products are methionine S-oxide and [Pt(CN)(4)](2-) as ident ified by NMR and UV spectroscopies, respectively. The kinetics is firs t order with respect to the platinum(Iv) and methionine concentrations and the I second-order rate constants have a small pH dependence. In analogy with reduction of platinum(rv) 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 thi oether group of methionine is assumed to interact with co-ordinated ha lide, 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 conc luded that methionine-containing biomolecules may compete with thiol c ompounds for reduction of platinum(rv) pro-drugs under acidic conditio ns, and also in neutral solutions with low, concentrations of thiol-co ntaining biomolecules.