Selective hydrolysis of the unactivated peptide bond in N-acetylated L-histidylglycine catalyzed by various palladium(II) complexes: dependence of the hydrolysis rate on the steric bulk of the catalyst

Hydrolytic reactions between various palladium(II) complexes of the type cis-[Pd(L)(H2O)(2)](2+) in which L is a chelating diamine (ethylenediamine, en; 1,2-propylenediamine, 1,2-pn; N-methylethylenediamine, Meen; isobutylenediamine, ibn and N,N,N',N'-tetramethylethylenediamine, Me,en) or S,N-coordinated amino acid (S-methyl L-cysteine, MeS-L-HCys and L-methionine, L-HMet) and N-acetylated L-histidylglycine (MeCO-His-Gly), were studied by H-1 MMR spectroscopy. The reactions were carried out in the pH range 2.0-2.5 and at 60 degrees C. In all these reactions, a palladium(II) complex bound to a histidine residue effects the regioselective cleavage of the amide bond involving the carboxylic group of histidine. We found that the rate of hydrolysis decreases as the steric bulk of the palladium(II) complex increases (en > 1,2-pn > Meen > MeS-L-HCys > ibn > L-HMet > Me(4)en). The observed rates of hydrolytic reaction are discussed in terms of steric hindrance of the chelating diamine or sulfur-containing amino acid on the palladium(II) complexes. This study is an important step in the development of new palladium(II) complexes as artificial metallopeptidases. (C) 2000 Elsevier Science Ltd All rights reserved.