Fast displacement of S,N-chelated l-methionine in platinum(II) complexes by biological thiols

The reactivity of [Pt(l-Met-S,N)2] (PtM2), a key metabolite of cisplatin, towards biological thiols glutathione (GSH) and l-cysteine (l-Cys) was investigated by HPLC, ESMS and 1H NMR techniques. The cis-isomer of PtM2 was found more reactive than the trans-isomer. The S,N-chelated l-methionine (l-MetH) can be readily displaced by both GSH and l-Cys, giving rise to the formation of thiolate-bridged polynuclear Pt(II) adducts. The substitution rate and the polymerization extent are highly dependent on pH values of the reaction solution.