[Pt(dien)]2+ migrates intramolecularly from methionine S to imidazole Nε2 in the peptides H-His-Gly-Met-OH and Ac-His-Ala-Ala-Ala-Met-NHPh

The pH- and time-dependent reaction of [Pt(dien)(H2O)](2+) with the methionine- and histidine containing peptides H-His-Gly-Met-OH and Ac-His-Ala-Ala-AIa-Met-NHPh at 313 K has been investigated by HPLC and NMR spectroscopy. For both peptides, initial relatively rapid formation of the kinetically favoured methionine S-bound complex is followed by slow intramolecular migration of the [Pt(dien)](2+) fragment to imidazole N-epsilon 2 (or, in the case of H-His-Gly-Met-OH, to a much lesser extent to the competing imidazole N-delta 1) of the histidine side chain over a period of 500 h. Time-dependent studies for the pentapeptide at pH8.0 demonstrate that this isomerization can take place by either direct S-->N-epsilon 2 migration or by a two-step mechanism involving initial N-epsilon 2 coordination of a second [Pt(dien)](2+) fragment and subsequent cleavage of the orginal Pt-S bond in the resulting dinuclear complex. The rate of kappa S/kappa N-epsilon 2 isomerization is markedly reduced on lowering the pH to 5.1.