RAPID, CATALYTIC HYDROLYSIS OF METHIONINE-CONTAINING DIPEPTIDES BY A DINUCLEAR PALLADIUM(II) COMPLEX HAVING THIOLATE BRIDGING LIGANDS

The dinuclear complex (Me4N)(2)[Pd-2(mu-SPh)(2)Cl-4] is solvolyzed upo n reaction with AgClO4 . H2O in acetone. The X-ray crystal structure o f (Ph4As)(2)[Pd-2(mu-SPh)(2)Cl-4] showed that this dinuclear complex i s bridged by two thiolate ligands with Cl- ions occupying terminal sit es on the palladium(II) atoms. The dinuclear solvolyzed species [Pd-2( mu-SPh)(2)(sol)(4)](ClO4)(2), in which sol is H2O 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 carb oxyl group of methionine. No prior activation of the amide bond is req uired for hydrolysis. Dipeptides with regular amide bonds are hydrolyz ed in nonaqueous solvents, under mild conditions. The reactions were f ollowed by H-1 NMR spectroscopy. Turnover was achieved with the follow ing N-acetylated dipeptides: AcMet-Gly, AcMet-Val, AcMet-Phe, and AcMe t-Ala One equivalent of [Pd-2(mu-SPh)(2)(sol)(4)](ClO4)(2) cleaves 6-1 4 equiv of dipeptide. The turnover number depends on the steric bulk o f the leaving amino acid. Hydrolysis kinetics were studied for AcMet-G ly, AcMet-Ala, AcMet-Val, AcMet-Phe, and AcMet-Leu. The reaction proce eds very rapidly, with a half-life of less than 7 min for AcMet-Ala at 50 degrees C. The half-lives at 40 degrees C for most of the dipeptid es are shorter than 30 min. Because the rate of the reaction also depe nds on the volume of the leaving amino acid, the catalyst is potential ly sequence-selective. The effects of temperature on the hydrolysis of AcMet-Ala were also studied. This study is a step toward the use of t ransition-metal complexes as reagents for the hydrolysis of lipophilli c peptides and proteins.