Dependence of hydrolytic cleavage of histidine-containing peptides by palladium(II) aqua complexes on the co-ordination modes of the peptides

Reactions of palladium(II) complexes cis-[PdCl 2 (en)] and cis-[PdCl 2 (L-HMet-S,N) ], in which en is ethane-1,2-diamine and methionine is an S,N-bidentate ligand, and their aqua analogs with dipeptides glycyl-L-histidine (Gly-His), L-histidylglycine (His-Gly), and the N-acetylated dipeptides MeCO-Gly-His and MeCO-His-Gly have been studied by 1 H NMR spectroscopy. In the reactions of cis-[PdCl 2 (L-HMet-S,N)] and cis-[PdCl 2 (en)] with Gly-His the formation of [Pd(Gly-His)(L-HMet-S)] + and [PdCl(Gly-His)] occurs at 1.5 < pH < 3.5. Tridentate co-ordination of Gly-His causes release of the en from cis-[PdCl 2 (en)] and ring opening of the L-HMet chelate in cis-[PdCl 2 (L-HMet-S,N) ]. The crystal structure of [PdCl(Gly-His)] shows that the peptide is bound to palladium(II) through imidazole N-3, amide, and amino nitrogen atoms. Tridentate chelation of Gly-His to palladium(II) is unfavorable for the hydrolysis of the peptide. The dipeptide His-Gly co-ordinates to palladium(II) as a bidentate ligand, via the imidazole N-3 and amino nitrogen atoms. This co-ordination mode also is unproductive for the hydrolysis of the peptide. However, at lower pH this complex converts into a hydrolytically active one, in which the dipeptide is bound to palladium(II) via the imidazole N-3 atom only. The dipeptides MeCO-His-Gly and MeCO-Gly-His, in which the terminal amino group is acetylated, exhibit more versatile co-ordination chemistry in the reactions with cis-[PdCl 2 (en)] and cis-[PdCl 2 (L-HMet-S,N)] and form complexes in which the imidazole N-1 atom co-ordinates to palladium(II). These studies with model complexes contribute to the understanding of selective cleavage of peptides and proteins by palladium(II) aqua complexes.