Peptide hydrolysis promoted by polynuclear and organometallic complexes of palladium(II) and platinum(II)

Several metal complexes promote selective hydrolytic cleavage of the methionine-alanine amide bond in the dipeptide AcMet-Ala; the amide bond in the N-acetylmethionyl moiety is not cleaved. The thioether group in the methionine side chain of the dipeptide cannot displace the stable 2-aminoethanethiolate ligand in the hexanuclear complex [Pd-2{Pd(aet)(2)}(4)](4+), and the dipeptide unattached to the complex does not hydrolyze. The thioether group in the side chain of the dipeptide displaces an ethylenediamine ligand in the tetranuclear complex [Pd-4(en)(4)(mu(2)-4,4'-bpy)(4)](8+), and cleavage in D2O occurs with the half-life of 2.0-3.5 h in the pH* range of 4.0-1.4. The thioether group in the dipeptide displaces an aqua ligand in the cycloocta-1,5-diene complexes cis-[Pt(cod)(D2O)(2)](2+) and cis-[Pd(cod)(D2O)(2)](2+), and cleavage in acetone-d(6) containing a small amount of D2O occurs with the half-lives of 0.20-20 h, depending on the peptide/complex mole ratio. This study shows that both coordination complexes and organometallic complexes can promote selective hydrolysis of peptide bonds and can do so even in solvents containing little water. This study is a step towards our ultimate goal-design of artificial metallopeptidases.