Steric effects on the rate of hydrolysis by palladium(II) complexes of the C-terminal amide bond in a series of methionine-containing dipeptides AcMet-Aa

A series of N-acetylated, methionine-containing dipeptides designated AcMet-Aa containing various C-terminal amino acids designated Aa are hydrolyzed in aqueous solution at 50 ºC and 0.95 < pD < 1.10 in the presence of three cis-[Pd(L)(H2O)2]2+ complexes, in which L are bidentate ligands en Me4en, and 3-OH-dtco. The reactions were monitored by 1H-NMR spectroscopy. The rate constant for hydrolytic cleavage of the Met-Aa bond decreases as the steric bulk of the amino acid Aa increases. Correlations to Taft’s Es values were made. The substituents on α-C and β-C atoms lower the rate constant most, those on the Ё-C atom lower it less, and those on the δ-C have no detectable effect. Partial selectivity for leaving amino acid Aa is attributed to differences in the volume of the side chain and to discrimination between leaving groups of similar volume but different branching patterns.