DEPENDENCE OF HYDROLYTIC CLEAVAGE OF HISTIDINE-CONTAINING PEPTIDES BYPALLADIUM(II) AQUA COMPLEXES ON THE COORDINATION MODES OF THE PEPTIDES

Reactions of palladium(II) complexes cis-[PdCl2(en)] and cis-[PdCl2(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-his tidine (Gly-His), L-histidylglycine (His-Gly), and the N-acetylated di peptides MeCO-Gly-His and MeCO-His-Gly have been studied by H-1 NMR sp ectroscopy. In the reactions of cis-[PdCl2(L-HMet-S,N)] and cis-[PdCl2 (en)] with Gly-His the formation of [Pd(Gly-His)(L-HMet-S)](+) and [Pd Cl(Gly-His)] occurs at 1.5 < pH < 3.5. Tridentate co-ordination of Gly -His causes release of the en from cis-[PdCl2(en)] and ring opening of the L-HMet chelate in cis-[PdCl2(L-HMet-S,N)]. The crystal structure of [PdCl(Gly-His)] shows that the peptide is bound to palladium(II) th rough imidazole N-3, amide, and amino nitrogen atoms. Tridentate chela tion of Gly-His;to palladium(II) is unfavorable for the hydrolysis;of the peptide. The dipeptide His-Gly co-ordinates ib 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 pep tide. However, at lower pH this complex converts into a hydrolytically active one, in which the dipeptide is bound to palladium(Ir) 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 versati le co-ordination chemistry in the reactions with cis-[PdCl2(en)] and c is-[PdCl2(L-HMet-S,N)] and form complexes in which the imidazole N-1 a tom 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.