kappa N-2(imidazole), S(thioether) macrochelation of [Pt(en)](2+) (en=H2NCH2CH2NH2) by terminal histidine and methionine side-chains in tri-, tetra- and penta-peptides

The pH and time dependent reactions of [Pt(en)(H2O)(2)](2+) (en = H2NCH2CH2 NH2) with the histidylmethionine peptides Hhis-gly-metH, Ac-his-gly-gly-met H [Ac = CH3C(O)] and Ac-his-ala-ala-ala-metH (Hgly = glycine, Hala = L-alan ine) at 313 K have been studied by ion-pairing reversed-phase HPLC and H-1 and Pt-195 NMR spectroscopy. Following initial anchoring of the [Pt(en)](2) fragment on the thioether S in a kappa(2)O,S complex, metallation of the neighbouring amide nitrogen is relatively rapid for all three peptides at p H < 4. After reaching a concentration maximum within 10-50 h, the resulting kappa(2)N'(met),S six-membered chelate slowly isomerizes to the thermodyna mically preferred kappa(2)N(1),S macrochelate and in the case of the tetra- and penta-peptides to the less favoured kappa(2)N(3),S complex as well. Th e speed of this reaction is significantly faster for the latter i + 4 spaci ng of the ligating residues, which brings the thioether S and imidazole don or atoms into close proximity for an a helix conformation. Although time de pendent studies indicated that the macrochelates are formed at a comparable rate to the kappa(2)N(met),'S complexes in alkaline solution, a clear ther modynamic preference for the smaller methionine chelate is apparent for the longer peptides.