Synergic effect of two metal centers in catalytic hydrolysis of methionine-containing peptides promoted by dinuclear palladium(II) hexaazacyclooctadecane complex

The species obtained by the reaction of Pd2(18]aneN6)Cl2](ClO4)2(where 18]aneN6 is 1,4,7,10,13,16-hexaazacyclooctadecane) with AgBF4 have been determined by electrospray ionization mass spectrometry (ESI-MS) to be an equilibrium mixture of three major types of dinuclear Pd(II) complex cations, Pd2(mu-O)(18]aneN6)]2+, Pd2(mu-OH)(18]aneN6)]3+ and Pd2(H2O)(OH)(18]aneN6)](3+), in aqueous solution. The hydroxo-group-bridged one, Pd2(mu-OH)(18]aneN6)]3+, is a dominant species, whose crystal structure has been obtained. The crystal structure of Pd2(mu-OH)(18]aneN6)](ClO4)3 shows that each Pd(II) ion in the dinuclear complex is tetra-coordinated by three nitrogen atoms and one hydroxo group bridge in a distorted square configuration. The two Pd(II) ions are 3.09 A apart from each other. The dinuclear Pd(II) complex cations Pd2(mu-OH)(18]aneN6)]3+ and Pd2(H2O)(OH)(18]aneN6)]3+ can efficiently catalyze hydrolysis of the amide bond involving the carbonyl group of methionine in methionine-containing peptides with turnover number of larger than 20. In these hydrolytic reactions, the two Pd(II) ions are synergic; one Pd(II) ion anchors to the side chain of methionine and the other one delivers hydroxo group or aqua ligand to carbonyl carbon of methionine, or acts as a Lewis acid to activate the carbonyl group of methionine, resulting in cleavage of Met-X bond. The binding constant of dinuclear Pd(II) complex cations with AcMet-Gly and AcMet were determined by 1H NMR titration to be 282 +/- 2 M(-1) and 366 +/- 4 M(-1), respectively. The relatively low binding constants enable the catalytic cycle and the possible catalytic mechanism is proposed. This is the first artificial mimic of metallopeptidases with two metal active centers.