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 pall adium(II) aqua complexes. The complexes cis-[Pd(en)(H2O)(2)](2+) (en = H2NCH2CH2NH2) and cis-[Pd(pn)(H2O)(2)](2+) (pn = H2NCH2CH2CH2NH2) yie ld [Pd-2(mu-MeCO-Met-Gly)(2)(H2O)(4)](4+) A, cis-[Pd(Met-S,N)(H2O)(2)] (2+) yields s-[Pd-2(mu-MeCO-Met-Gly)(2)(H2O)(2)(HMet)(2)](6+), B and t rans-[Pd-2{Cys(Me)-S,N}(2)(H2O)(2)](4+) [Cys(Me) = S-methylcysteine] y ields Pd-2{mu-HCys(Me)}(2)(H2O)(2)(MeCO-Met-Gly)(2)](6+) C. The comple x 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 hydrolyti c cleavage of the methionine-glycine amide bond in the co-ordinated Me CO-Met-Gly are conveniently monitored by H-1 NMR spectroscopy. The rat e of cleavage decreases in the order A > B approximate to C > D, in wh ich the number of aqua ligands per peptide ligand decreases. Intramole cular attack by aqua ligands;is more efficient than external attack by water molecules from the solvent. The peptide ligands occupying termi nal and bridging positions in the binuclear palladium(II) complexes un dergo hydrolysis at similar rates. This study shows the importance of polynuclear metal complexes in hydrolytic cleavage of peptide bonds.