pH-Dependent competition between N,S and N,N′ chelation in the reaction of [Pt(en)(H2O)2]2+ (en = H2NCH2CH2NH2 ) with methionine-containing di- and tri-peptides

Abstract

Products of the reaction of the cisplatin analogue [Pt(en)(H ₂ O) ₂ ] ²⁺ (en = ethane-1,2-diamine) with methionine (Hmet)-containing di- and tri-peptides in the range pH 2.5–11.0 have been separated by semi-preparative reversed-phase HPLC with perfluorinated carboxylic acids as ion-pairing agents. Structural characterisation of the (en)Pt ^II complexes of met-Hxaa (met-Hgly, met-gly-Hgly) and xaa-Hmet (gly-Hmet, gly-met-Hgly, gly-gly-Hmet) peptides with respectively N-terminal methionine or glycine (Hgly) units was achieved by multinuclear NMR spectroscopy. The κ ² N (amino),S (thiother) and κ ² N (amino),N′ (amide) chelation modes are competitive for met-Hxaa peptides with the former mode predominating at pH < 8.7, the latter at higher pH. In contrast, κ ² N′ (amide),S (thioether)-co-ordinated species are observed for xaa-Hmet peptides in acid solution with cleavage of a Pt–N (en) bond leading to competitive κ ³ N (amino),N′ (amide),S (thioether) complexes for gly-Hmet and gly-met-Hgly. At pH > 7.4, the κ ² N,N′ complexes dominate for these bioligands as for met-Hxaa peptides. This is not the case for gly-gly-Hmet, for which only one major species with κ ² N″ (amide),S (thioether) co-ordination is found at pH < 10.6.