Studies of Copper Complexes Displaying N₃S Coordination as Models for Cu_BCenter of Dopamine β-Hydroxylase and Peptidylglycine α-Hydroxylating Monooxygenase

Abstract

We describe the studies of new copper complexes [MeSPY2]CuPF(6), 2, and [MeSPY2]Cu(ClO(4))(2).CH(3)CN, 3, as models for the Cu(B) center of dopamine beta-hydroxylase and peptidylglycine alpha-hydroxylating monooxygenase. The structure of [MeSPY2]Cu(ClO(4))(2).CH(3)CN, 3, has been established by X-ray crystallography. The copper coordination exhibits a square pyramidal geometry where the equatorial plane is occupied by the SCH(3) group and three nitrogen atoms (tertiary amine, one pyridine, and acetonitrile solvent), whereas the axial position binds the second pyridine. Using FEFF calculations and multiscattering interaction, EXAFS refinements show that the SMe group lies in the coordination sphere of copper complexes [MeSPY2]CuPF(6), 2, and [MeSPY2]Cu(ClO(4))(2).CH(3)CN, 3. While [MeSPY2]CuPF(6), 2, reacts with dioxygen in dichloromethane without oxidation of the ligand, we observed an oxidation of the sulfide ligand when [MeSPY2]Cu(ClO(4))(2).CH(3)CN, 3, reacts with hydrogen peroxide in methanol. Considering results, we propose that Met(314), crucial for DBH and PHM activity, could be the site of the H(2)O(2) (or ascorbate) inactivation by oxidation to the sulfoxide group.

Sulfur ligation in copper enzymes and models

“…To understand the possible involvement of the methionine ligand different copper(II) complexes with N3S-type ligand have been prepared in the literature [46][47][48]. A questioning model has been described by Réglier et al [46].…”

“…A questioning model has been described by Réglier et al [46]. The complex [MeSPY2Cu](ClO 4 ) 2 AE CH 3 CN (Fig.…”

“…Mechanism proposed[46] for hydrogen peroxide reaction in methanol of [MeSPY2Cu](ClO 4 ) 2 AE CH 3 CN, model complex for DbM and PHM.…”

N-Hydroxyguanidines oxidation by a N3S copper-complex mimicking the reactivity of Dopamine β-Hydroxylase

“…Spectroscopic studies have shown that two copper ions are present at the active site of DBH with different coordination spheres in the oxidized and reduced states [22][23][24]. Recently, the water-soluble Cu(II) complex Py 2 SMeCu(II) 8 has emerged as a good model of the N 3 S coordination sphere of the Cu B center of DBH with a reactivity mimicking that of the enzyme [25].…”

A cofactor approach to copper-dependent catalytic antibodies

“…Substantial rate accelerations for hydrolysis, particularly of carboxylic acid esters, have been attained with some of these model Cu(II) and Zn(II) complexes (33)(34)(35)(36). Although Cu complexes, which reasonably mimic the structural and spectroscopic features of the Cu-hydroxylases, have been prepared (37)(38)(39)(40), few possess polyimidazole ligands or have been shown to promote the hydroxylation of relevant substrates (usually stoichiometric hydroxylation of their own ligands is a major problem) (41)(42)(43)(44), and none of these reactions are catalytic.…”