Galactose oxidase copper complexes

Fig. 8. Tyrosine coordination modes in galactose oxidase-copper complex. Tyrosine phenolate bond angles (0) and ring torsion angles (t) are indicated. (Based on protein coordinates PDB ID IGOG.)...

Galactose oxidase copper(II) complexes, 723 copper(III) complexes, 749 Gattermann-Koch reaction, 568 Glycosidation... 

A number of complexes of copper with 1,1-dithiolenes are known they are interesting, inasmuch as they form (1) polynuclear species, e.g., [Cu4(i-mnt)3]2 . Recently, a copper(III) complex of 1,1-dicarboeth-oxy-2-ethylenedithiolate (DED ) was prepared (375) by oxidation of aqueous solutions of K2[Cu(DED)2] with a 10-15% excess of Cu(II) or H202, and of (BzPh3P)2[Cu(DED)2] with I2. The possibility of this system as a model for the Cu "/Cu. system in n-galactose oxidase has been pointed out. Lewis and Miller (113) also prepared M[Cu(S2C CHN02)2] (M = Cu, or Zn) and Cu[Cu S2C C(CN)2 2], and found that they are effective insecticides. 

Copper(II) complexes with phenoxo ligands have attracted great interest, in order to develop basic coordination chemistry for their possible use as models for tyrosinase activity (dimeric complexes) and fungal enzyme galactose oxidase (GO) (monomeric complexes). The latter enzyme catalyzes the two-electron oxidation of primary alcohols with dioxygen to yield aldehyde and... 

Interest is mounting in this state, promoted once again by its possible implication in biological systems. Galactose oxidase, for example, is a copper enzyme which catalyses the oxidation of galactose to the corresponding aldehyde. The tervalent oxidation state may be prepared from Cu(II) by chemical, anodic and radical oxidation. Cu(III) complexes of peptides and macrocycles have been most studied, particularly from a mechanistic viewpoint. The oxidation of I" by Cu(III)-deprotonated peptide complexes and by imine-oxime complexes have a similar rate law... 

There are numerous reports on the chemical synthesis of models for the active site of galactose oxidase both in the reduced Cu(l) and the oxidized Cu(II) form. We mention only a selection in which EPR is at least used to characterize the complex either on the phenoxy radical or on the copper part, typically in conjunction with X-ray data.48,49 50 A review on structural, spectroscopic and redox aspects of galactose oxidase models is available.51 More important with respect to EPR is the report on the 3-tensor calculation of the thioether substituted tyrosyl radical by ab initio methods but this is borderline to the aspects treated in this review since the copper ion is not involved.52... 

The paramagnetic copper present in the non-blue oxidases such as galactose oxidase and amine oxidases, and also in the blue oxidases, has d-d and ESR spectra typical of coordination complexes of copper(II). 

Hamilton and co-workers (27, 28) have suggested Cu(III) as a probable intermediate in the reaction catalyzed by galactose oxidase. Papers by Kosman and co-workers (29, 30) seem at variance with this interpretation. Regardless of the outcome of this dispute, we hope that our evidence for the existence and properties of Cu(III)—peptide complexes will encourage more investigations of the presence of trivalent copper in biological systems. Our work shows that this oxidation state is readily attained under biological conditions. 

Galactose oxidase hinds a single copper ion within Domain 11 on the axis of the wheel. The active site (Fig. 5) is unhke any other biological copper complex, an appropriate distinction for this remarkable enzyme. To explore the site in more detail, the protein environment of the mononuclear copper center may be separated into (A) direcdy coordinated metal hgands (hrst shell, inner sphere interactions) and (B) the extended active site environment (the second shell or outer coordination sphere). 

Jazdzewski, B. A., Young, V. G. jr., and Tolman, W. B., 1998, A Three-Coordinate Copper(I)-Phenoxide Complex that Models the Reduced Form of Galactose Oxidase, Chem. Commun. 1998 2521n2522. 

Sokolowski, A., Leutbecher, H., Weyherm,ller,T., Schnepf, R., Bothe, E., Bill, E., Hildenbrandt, P., and Wieghardt, K., 1997, Phenoxyl-Copper (II) Complexes Models for the Active Site of Galactose Oxidase, J. Biol. Inorg. Chem. 2 444n453. 

Zurita, D., Gautier-Luneau, L, MEnage, S., Pierre, J.-L., and Saint-Aman, E., 1997, A First Model for the Oxidized Active Form of the Active Site of Galactose Oxidase a Free Radical Copper Complex, J. Biol. Inorg. Chem. 2 46n55. 

The copper complex of the diaminodiol (98) functions as a model foT galactose oxidase.A related diamidodiol (99) has been reported binding to high-valent Os and Ru, as well as in mixed [Cu L M(bipy)2] (M = Co, Ni, Zn) compounds, some of the latter being antiferromagnetically coupled. A number of diamine-diacid ligands have appeared, such as (100), ... 

Stack and co-woikers [25] have synthesized model complexes that resemble both the spectroscopic characteristics and the catalytic activity of galactose oxidase. For these complexes, EXAFS and edge XAS experiments indicate that the radical is most likely located axially in the non-square planar coordination of the copper. Calculations by Rothlisberger and Carloni [26] on these model systems confirm this fact. We also recommend the chapter herein by that group, in which the fuU reaction mechanism of GO has been investigated using Car-ParineUo MD methods. 

As a mimic of the well-studied galactose oxidase [37], a copper(II) thiophenol complex catalyzes the oxidation of primary alcohols to aldehydes in the presence of (Scheme 12) [38]. The latter also promotes the oxidation of secondary alcohols to diols (Scheme 12). The catalytic cycle starts with the oxidation of copper by O, leading to a biradical species. The intermediate 39 is produced from 38 by coordination of two alkoxide substrates. The rate-limiting step is the formation of 40 from 39 by a hydrogen atom transfer from the secondary alcoholate to the oxygen-centered radicals of the aminophenols ligands. The cycle is then closed by radical dimerization which leads the formation of the diol [39]. 

Copper(m)—A copper(iii) complex of the enzyme galactose oxidase has been postulated as the active intermediate in the oxidation of D-galactose. Autoxidation of copper(ii)-peptide complexes leads to relatively long-lived copper(iii)-peptide species. ... 

This compound was the first example of a three-coordinate complex of copper(II) outside a protein environment, and it is a precursor to other three-coordinate copper(II) complexes.1 The chloride ligand in this complex has been substituted with thiolate and phenolate ligands to give mimics of type 1 copper sites1,2 and of reduced galactose oxidase,3 respectively. Itoh and Tolman have examined the influence of diketiminate substitution pattern on the copper(II) chemistry.4... 

Since both alcoholic oxidation and O2 reduction are two-electron processes, the catalytic reaction is conceptually equivalent to a transfer of the elements of dihydrogen between the two substrates. Biological hydrogen transfer generally involves specialized organic redox factors (e.g., flavins, nicotinamide, quinones), with well-characterized reaction mechanisms. Galactose oxidase does not contain any of these conventional redox factors and instead utilizes a very different type of active site, a free radical-coupled copper complex, to perform this chemistry. The new type of active site structure implies that the reaction follows a novel biochemical redox mechanisms based on free radicals and the two-electron reactivity of the metalloradical complex. 

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