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

Abstract

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(μ-O)([18]aneN₆)]²⁺, [Pd₂(μ-OH)([18]aneN₆)]³⁺ and [Pd₂(H₂O)(OH)([18]aneN₆)]³⁺, in aqueous solution. The hydroxo-group-bridged one, [Pd₂(μ-OH)([18]aneN₆)]³⁺, is a dominant species, whose crystal structure has been obtained. The crystal structure of [Pd₂(μ-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 Å apart from each other. The dinuclear Pd(II) complex cations [Pd₂(μ-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.