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 H-1 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. (C) 2004 Published by Elsevier B.V.