Iryna A. Koval

Synthetic models of the active site of catechol oxidase: mechanistic studies

The ability of copper proteins to process dioxygen at ambient conditions has inspired numerous research groups to study their structural, spectroscopic and catalytic properties. Catechol oxidase is a type-3 copper enzyme usually encountered in plant tissues and in some insects and crustaceans. It catalyzes the conversion of a large number of catechols into the respective o-benzoquinones, which subsequently auto-polymerize, resulting in the formation of melanin, a dark pigment thought to protect a damaged tissue from pathogens. After the report of the X-ray crystal structure of catechol oxidase a few years earlier, a large number of publications devoted to the biomimetic modeling of its active site appeared in the literature. This critical review (citing 114 references) extensively discusses the synthetic models of this enzyme, with a particular emphasis on the different approaches used in the literature to study the mechanism of the catalytic oxidation of the substrate (catechol) by these compounds. These are the studies on the substrate binding to the model complexes, the structure-activity relationship, the kinetic studies of the catalytic oxidation of the substrate and finally the substrate interaction with (per)oxo-dicopper adducts. The general overview of the recognized types of copper proteins and the detailed description of the crystal structure of catechol oxidase, as well as the proposed mechanisms of the enzymatic cycle are also presented.

New didentate bispyrazole ligands forming uncommon eight-ring chelates with divalent copper, zinc and cobalt

Abstract The novel ligands 1,3-bis(pyrazol-1′-yl)propane (bpp) and 1,3-bis(3′,5′-dimethylpyrazol-1′-yl)propane (bdpp) have been prepared by reacting 2 equiv. of the corresponding potassium pyrazolate with 1 equiv. of 1,3-dibromopropane. Compound 1,3-bis(5′-methylpyrazol-1′-yl)propane (bmpp) has been prepared from bpp by lithiation at the five position and the subsequent addition of iodomethane. These new ligands form M(II) coordination compounds with the general formula [M(ligand)X2] where X=Cl or NO3, and M=Cu, Zn, or Co. The single-crystal X-ray structures of [Cu(bmpp)(NO3)2], [Cu(bdpp)Cl2], [Zn(bdpp)Cl2], and [Zn(bpp)Cl2] show the ligands to act as didentate chelates forming an uncommon eight-atom chelate ring with the metal ion. In [Cu(bmpp)(NO3)2] each copper ion is distorted octahedrally surrounded, whereas the metal ions in the chloride complexes have distorted tetrahedral geometries. The spectral properties are in accord with the structural data.

Catecholase activity of a μ-hydroxodicopper(II) macrocyclic complex: structures, intermediates and reaction mechanism

The monohydroxo-bridged dicopper(II) complex (1), its reduced dicopper(I) analogue (2) and the trans-μ-1,2-peroxo-dicopper(II) adduct (3) with the macrocyclic N-donor ligand [22]py4pz (9,22-bis(pyridin-2′-ylmethyl)-1,4,9,14,17,22,27,28,29,30- decaazapentacyclo -[22.2.114,7.111,14.117,20]triacontane-5,7(28),11(29),12,18,20(30), 24(27),25-octaene), have been prepared and characterized, including a 3D structure of 1 and 2. These compounds represent models of the three states of the catechol oxidase active site: met, deoxy (reduced) and oxy. The dicopper(II) complex 1 catalyzes the oxidation of catechol model substrates in aerobic conditions, while in the absence of dioxygen a stoichiometric oxidation takes place, leading to the formation of quinone and the respective dicopper(I) complex. The catalytic reaction follows a Michaelis–Menten behavior. The dicopper(I) complex binds molecular dioxygen at low temperature, forming a trans-μ-1,2-peroxo-dicopper adduct, which was characterized by UV–Vis and resonance Raman spectroscopy and electrochemically. This peroxo complex stoichiometrically oxidizes a second molecule of catechol in the absence of dioxygen. A catalytic mechanism of catechol oxidation by 1 has been proposed, and its relevance to the mechanisms earlier proposed for the natural enzyme and other copper complexes is discussed.

New dinuclear Co(II) and Mn(II) complexes of the phenol-based compartmental ligand containing formyl and amine functions: structural, spectroscopic and magnetic properties

The phenol-based compartmental ligand Hpy2ald contains a tridentate amino arm and a weak donor aldehyde group at the 2 0 and at the 6 0 positions of the phenol ring, respectively. This ligand reacts with cobalt(II) perchlorate, cobalt(II) tetrafluoroborate and manganese(II) perchlorate, yielding dinuclear complexes, where two metal ions are doubly bridged by two deprotonated cresolate moieties. The coordination environment around the metal ions is then completed to a very distorted octahedron by three nitrogen donor atoms from the pendant amino arm and the oxygen atom of the aldehyde group. The crystal structures of the complexes, their spectroscopic and magnetic properties are reported. 2003 Elsevier B.V. All rights reserved.

Dinuclear copper(II) complexes of four new pyrazole-containing macrocyclic ligands are active catalysts in the oxidative coupling of 2,6-dimethylphenol

Four new macrocyclic ligands of varying ring size, [22]py4pz, [22]pr4pz, [18]py2pz and [20]py2pz, containing four or two endocyclic pyrazole groups, form dinuclear copper compounds. The single crystal X-ray structures of [Cu(pr2pz)(ClO4)2 ]( A), [Cu2([22]pr4pz)Cl4](MeOH) (B), [Cu4([18]py2pz)2(m-Cl)4Cl2]Cl2 (C) and [Cu2([18]py2pz)(CH3CN)4(ClO4)2](ClO4)2(CH3CN)1.6 (D), show the pyrazole groups and the amine nitrogens all to be involved in the coordination of the copper(II) ions. In the mononuclear compound A the copper ion is in a distorted octahedral geometry, with the equatorial plane formed by four nitrogen donor atoms from the ligand and the axial positions occupied by two oxygen atoms from mono-coordinated perchlorate anions. In compound B each copper ion is in a distorted square pyramidal environment, with the three ligand nitrogens and a chloride atom in the equatorial plane and another chloride atom in the axial position. The cation of compound C contains four copper centers. Two bridging Cl atoms connect the two central copper atoms to form a centrosymmetric four membered ring. Two macrocyclic units are present in the cation, each containing two copper atoms bridged by a chloride atom. One copper is fivefold coordinated and the second copper is distorted octahedral. In compound D both copper(II) ions are in a distorted octahedral N5 Oe nvironment, with the equatorial plane formed by the three ligand nitrogens and a nitrogen from an acetonitrile molecule. A second acetonitrile molecule and a mono-coordinated perchlorate anion are weakly bound in the axial positions. The copper nitrate compounds of these new ligands are to some degree active catalysts in the oxidative coupling of 2,6-dimethylphenol with molecular dioxygen to poly(2,6-dimethyl1,4-phenylene ether). # 2003 Elsevier B.V. All rights reserved.

Bio-mimicking galactose oxidase and hemocyanin, two dioxygen-processing copper proteins

The modelling of the active sites of metalloproteins is one of the most challenging tasks in bio-inorganic chemistry. Copper proteins form part of this stimulating field of research as copper enzymes are mainly involved in oxidation bio-reactions. Thus, the understanding of the structure-function relationship of their active sites will allow the design of effective and environmental friendly oxidation catalysts. This perspective illustrates some outstanding structural and functional synthetic models of the active site of copper proteins, with special attention given to models of galactose oxidase and hemocyanin.

Changes in magnetic properties from solid state to solution in a trinuclear linear copper(II) complex

A linear trinuclear copper(II) complex containing phenoxido- and alkoxido-bridges between the metal centers has been isolated and structurally characterized. The complex cation consists of a linear array of three copper ions, assembled by means of two doubly deprotonated ligands. The octahedral coordination sphere of the two peripheral copper(II) ions is completed by weakly bound methanol molecules, and the square-planar central metal ion is located on an exact, crystallographic inversion center. Temperature-dependent magnetic susceptibility studies reveal the presence of antiferromagnetic exchange coupling between the copper(II) ions in the trinuclear unit along with small intermolecular antiferromagnetic interactions in the low temperature range. The results were fitted in two different ways, (i) taking into account solely the exchange interaction between the adjacent metal centers or, (ii) regarding exchange interactions between both adjacent and non-adjacent copper(II) ions. Solid-state temperature-dependent X-band EPR studies in the range 4.2–250 K indicate a doublet ground spin state |½, 1〉. In solution, the ground spin state of the complex is found to be a quartet (S = ), suggesting a modification of the exchange coupling interactions between the copper(II) ions. The simulation of the 4.2 K solution spectrum gives rise to the best parameters D > 0.8 cm−1, g⊥ = 2.04 and g∥ = 2.21.

Unprecedented copper(II)-assisted acetal formation of a formyl-substituted bispyrazole. The X-ray structures of copper[1,2-bis(3′-dimethoxymethylpyrazol-1′-yl)ethane] dichloride and dibromide

The formation of two new acetal-containing ligands 1,2-bis(3′-dimethoxymethylpyrazol-1′-yl)ethane (bdmpe) and 1,2-bis(3′-diethoxymethylpyrazol-1′-yl)ethane (bdepe) in a Cu(II)-assisted alcoholysis of the initial ligand 1,2-bis(3′-formylpyrazol-1′-yl)ethane is described. The new ligands form polymeric complexes with Cu(II) salts of the general formula [Cu(L)X2]x, where L = bdmpe or bdepe, and X = Cl or Br. The single-crystal X-ray structures of [Cu(bdmpe)Cl2]x and [Cu(bdmpe)Br2]x show that two of the four oxygen atoms of the acetal fragments are axially semi-coordinated to the copper(II) ions, adjusting the coordination sphere around the metal ion to a very distorted octahedron. The coordination of the oxygen atoms of the acetal groups to the metal ion may well be the driving force for the transformation of the initial aldehyde groups into the acetal fragments. The equatorial plane in [Cu(bdmpe)Cl2]x is a trans-CuN2Cl2 chromophore, while in [Cu(bdmpe)Br2]x it is a cis-CuN2Br2 species with a large in-plane distortion.