#kappa#~2N(imidazole), S(thioether) Macrochelation of [Pt(en)]~(2+) (en=H_2NCH_2CH_2NH_2) by terminal histidine and methionine side-chains in tri-, tetra- and penta-peptides

摘要

The pH and time dependent reactions of [Pt(en)(H_2O_2)]~(2+) (en=H_2NCH_2CH_2NH_2) with the histidylmethionine peptides Hhis-gly-metH, Ac-his-gly-gly-metH [Ac=CH_3C(O)] and Ac-his-ala-ala-ala-metH (Hgly=glycine, Hala=L-alanine) at 313 K have been studied by ion-pairing reversed-phase HPLC and ~1H and ~(195)Pt NMR spectroscopy. Following initial anchoring of the [Pt(en)]~(2+) fragment on the thioether S in a #kappa#~2O, S complex, metallation of the neighbouring amide nitrogen is relatively rapid for all three peptides at pH<4. After reaching a concentration maximum within 10-50 h, the resulting #kappa#~2N'_(met), S six-membered chelate slowly isomerizes to the thermodynamically preferred #kappa#~2N~1, S macrochelate and in the case of the tetra- and penta-peptides to the less favoured #kappa#~2N~3, S complex as well. The speed of this reaction is significantly faster for the latter i+4 spacing of the ligating residues, which brings the thioether S and imidazole donor atoms into close proximity for an #alpha# helix conformation. Although time dependent studies indicated that the macrochelates are formed at a comparable rate to the #kappa#~2N'_(met), S complexes in alkaline solution, a clear thermodynamic preference for the smaller methionine chelate is apparent for the longer peptides.