Rapid, Catalytic Hydrolysis of Methionine-Containing Dipeptides by a Dinuclear Palladium(II) Complex Having Thiolate Bridging Ligands

The dinuclear complex (Me 4 N) 2 [Pd 2 (μ-SPh) 2 Cl 4 ] is solvolyzed upon reaction with AgClO 4 ·H 2 O in acetone. The X-ray crystal structure of (Ph 4 As) 2 [Pd 2 (μ-SPh) 2 Cl 4 ] showed that this dinuclear complex is bridged by two thiolate ligands with Cl - ions occupying terminal sites on the palladium(II) atoms. The dinuclear solvolyzed species [Pd 2 (μ-SPh) 2 (sol) 4 ](ClO 4 ) 2, in which sol is H 2 O or acetone, binds to methionine side chains in AcMet-X, where X is Gly, Ala, Leu, Phe, or Val. It then catalyzes hydrolysis of the amide bond involving the carboxyl group of methionine. No prior activation of the amide bond is required for hydrolysis. Dipeptides with regular amide bonds are hydrolyzed in nonaqueous solvents, under mild conditions. The reactions were followed by 1 H NMR spectroscopy. Turnover was achieved with the following N-acetylated dipeptides: AcMet-Gly, AcMet-Val, AcMet-Phe, and AcMet-Ala. One equivalent of [Pd 2 (μ-SPh) 2 (sol) 4 ](ClO 4 ) 2 cleaves 6−14 equiv of dipeptide. The turnover number depends on the steric bulk of the leaving amino acid. Hydrolysis kinetics were studied for AcMet-Gly, AcMet-Ala, AcMet-Val, AcMet-Phe, and AcMet-Leu. The reaction proceeds very rapidly, with a half-life of less than 7 min for AcMet-Ala at 50 °C. The half-lives at 40 °C for most of the dipeptides are shorter than 30 min. Because the rate of the reaction also depends on the volume of the leaving amino acid, the catalyst is potentially sequence-selective. The effects of temperature on the hydrolysis of AcMet-Ala were also studied. This study is a step toward the use of transition-metal complexes as reagents for the hydrolysis of lipophillic peptides and proteins.