Kinetic study of stereochemical and other factors governing hydrolytic cleavage of a peptide ligand in binuclear palladium(II) complexes

The dipeptide N-acetylmethionylglycine (MeCO-Met-Gly) reacted, via the thioether group in the methionyl side chain, with five different palladium(II) aqua complexes. The complexes cis-[Pd(en)(H2O)(2)](2+) (en = H2NCH2CH2NH2) and cis-[Pd(pn)(H2O)(2)](2+) (pn = H2NCH2CH2CH2NH2) yield [Pd-2(mu-MeCO-Met-Gly)(2)(H2O)(4)](4+) A, cis-[Pd(Met-S,N)(H2O)(2)](2+) yields trans-[Pd-2(mu-MeCO-Met-Gly)(2)(H2O)(2)(HMet)(2)](6+), B and trans-[Pd-2{Cys(Me)-S,N}(2)(H2O)(2)](4+) [Cys(Me) = S-methylcysteine] yields trans-[Pd-2{mu-HCys(Me)}(2)(H2O)(2)(MeCO-Met-Gly)(2)](6+) C. The complex cis-[Pd(dtco)(H2O)(2)](2+) (dtco = 1,5-dithiacyclooctane) yields [Pd-2(mu-MeCO-Met-Gly)(2)(dtco)(2)](4+), D. These reactions and hydrolytic cleavage of the methionine-glycine amide bond in the co-ordinated MeCO-Met-Gly are conveniently monitored by H-1 NMR spectroscopy. The rate of cleavage decreases in the order A > B approximate to C > D, in which the number of aqua ligands per peptide ligand decreases. Intramolecular attack by aqua ligands;is more efficient than external attack by water molecules from the solvent. The peptide ligands occupying terminal and bridging positions in the binuclear palladium(II) complexes undergo hydrolysis at similar rates. This study shows the importance of polynuclear metal complexes in hydrolytic cleavage of peptide bonds.