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(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.

Major Advances in the Hydrolysis of Peptides and Proteins by Metal Ions and Complexes

“…Notwithstanding, recent pioneering studies by the research groups of Kostić [41][42][43]70,71,73,76,77,79,[81][82][83]85,86], Zhu [88], and Sheldrick [51] have proven palladium(II) and platinum(II) complexes to be extremely useful reagents for the sequencespecific hydrolysis of peptides. Although Pt II is substitutionally inert, Pd II is more labile and turnover is possible.…”

A dipalladium complex with a single hydroxo bridge and its methylpalladium precursor

“…Another less obvious difference is that the hydroxo ligand is involved in hydrogen bonding in 2 (Fig. 3) but, unusually, 4,5 not in H. 8 An important question is to what extent these large differences between the structures of 2 and H are due to the presence of the cyclam ligand in H or the relatively bulky bpma ligand in 2. In order to elucidate this issue, calculations using DFT theory were carried out on the cations 2, H and on the simple model cations [M 2 (m-OH)(NH 3 ) 6 ] 3+ , G (Scheme 2, M = Pd or Pt, L = NH 3 ).…”

“…[1][2][3][4][5][6][7][8] A comparison of some structural features is given in Table1. The most dramatic difference between complexes 2 and H is the Pd-O-Pd bond angle which is 95.9(3) • in H but 141.2(3) • in 2, a difference of 45.6 • .…”

Progress in Designing Artificial Proteases: A New Therapeutic Option for Amyloid Diseases

“…[29] For peptide hydrolysis of various methionine derivatives by dinuclear Pd 2 + complex 27, it was proposed that one Pd 2 + cleaves the peptide bond, whereas the other Pd 2 + binds to the sulfur atom of Met of the substrate. [30] Organic pendants attached to metal complexes have been used as binding sites. Ammonium groups are exposed on the surface of soluble proteins.…”