Reactions of cisplatin hydrolytes with methionine, cysteine, and plasma ultrafiltrate studied by a combination of HPLC and NMR techniques

The reactions of cis-[PtCl(NH3)(2)(H2O)](+) with L-methionine have been stu died by 1D Pt-195 and N-15 NMR, and by 2D[H-1, N-15] NMR, When the platinum complex is in excess, the initial product, cis-[PtCl(NH3),(Hmet-S)](+) und ergoes slow ring closure to [Pt(NH3)(2)(Hmet-N,S)](2+) . Slow ammine loss t hen occurs to give the isomer of [PtCl(NH3) (Hmet-N,S)](+) with chloride ha ns to sulfur. When methionine is in excess, a reaction sequence is proposed in which trans-[PtCl(NH3) (Hmet-S)(2)](+) isomerises to the cis-isomer, wi th subsequent ring closure reactions leading to cis-[Pt(Hmet-N,S)(2)](2+). Near pH 7, methionine is unreactive toward cis-[PtCl(OH) (NH3)(2)]. By cont rast, L-cysteine reacts readily with cis- [PtCl(OH) (NH3)(2)] at pH7, but t here were many reaction products, including bridged species. Cis-[PtCl(OH) (NH3)(2)] reacts with reduced thiols in ultrafiltered plasma but these are oxidized if the plasma is not fresh or appropriately stored. With very low concentrations of the platinum complexes (35.5 mu M), HPLC experiments (UV detection at 305 nm) indicate that the thiolate (probably cysteine) reactio ns become simpler as bridging becomes less important. (C) 1999 Elsevier Sci ence Inc. All rights reserved.