Copper complexes peptides

Copper-peptide complexes have been the most extensively studied of all the metal-peptide complexes. Copper(II) is the most important oxidation state in copper-peptide complexes, although copper(III) can be stabilized by coordination to peptides. The deprotonated peptide nitrogens help stabilize the higher oxidation state of copper therefore the more deprotonated peptide nitrogens, the more stable the copper(III) complex. Copper(III) complexes are generally prepared by electrochemical oxidation of the copper(II) complex at pH 10 or higher. 

Table 2 Reactions of copper peptide complexes with nucleophiles at 25 °C, /= 0.1 M...

The kinetics and mechanisms of substitution reactions of metal complexes are discussed with emphasis on factors affecting the reactions of chelates and multidentate ligands. Evidence for associative mechanisms is reviewed. The substitution behavior of copper(III) and nickel(III) complexes is presented. Factors affecting the formation and dissociation rates of chelates are considered along with proton-transfer and nucleophilic substitution reactions of metal peptide complexes. The rate constants for the replacement of tripeptides from copper(II) by triethylene-... 

The sluggish substitution properties of copper(III) and nickel(III) peptide complexes have permitted the isolation of complexes with these oxidation states (14, 15). Thus, the tri-valent peptide complexes pass through a cation exchange resin which readily strips copper(II) or nickel(II) from the corresponding complexes. We now have a little more information about the substitution characteristics of the trivalent metal complexes. 

E. L. Hegg, J. N. Burstyn, Hydrolysis of Unactivated Peptide Bonds by a Macrocyclic Copper(II) Complex Cu([9]aneN3)Cl2 Hydrolyzes Both Dipeptides and Proteins , J. Am. Chem. Soc. 1995, 117, 7015-7016. 

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... 

The blue color of these "type 1" copper proteins is much more intense than are the well known colors of the hydrated ion Cu(H20)42+ or of the more strongly absorbing Cu(NH3)42+. The blue color of these simple complexes arises from a transition of an electron from one d orbital to another within the copper atom. The absorption is somewhat more intense in copper peptide chelates of the type shown in Eq. 6-85. However, the -600 nm absorption bands of the blue proteins are an order of magnitude more intense, as is illustrated by the absorption spectrum of azurin (Fig. 23-8). The intense blue is thought to arise as a result of transfer of electronic charge from the cysteine thiolate to the Cu2+ ion.520 521... 

Biuret Reaction. The particular capabilities of the stop-ped-flow vidicon system have been used to help explain some unusual behavior in the biuret reaction. The biuret reaction is the basis for the standard clinical chemistry technique for determining the total protein content of human blood serum (23). It involves a complexation reaction, in alkaline solution, between the cupric ion (Cu2+) and the peptide bonds of the protein. In the standard biuret technique, the reaction is allowed to go to completion and then the absorbance of the copper-protein complex is measured at 55 nm. This technique tends to be rather slow since the reaction, although very rapid over the first few seconds, does not go to completion for at least 20 to 30 minutes. 

Cyclic peptides can be viewed as a step on the way from the modeling of unconstrained peptides to folded proteins. The copper(II) complex of a cyclic octapep-tide has been investigated by molecular mechanics and EPR spectroscopy and the structure was found to be in accord with those of closely related complexes 205]. Similar combined approaches are also applicable to metalloproteins. 

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. 

Copper(II) d-d Absorption Band. Billo (42) correlated spectral data for the Cu( II)-peptide complexes with the type of coordinated groups. The wavelength of the absorbance band observed between 500 and 740 nm varies with the number of deprotonated peptide groups and amine groups. The vmax(kK) of the d-d band (aqueous solution spectra) can be expressed as the sum of the individual ligand field contribution of the four donor atoms which define the square plane with copper. In Equation 3 the ns refer to the number of each type of donor atom... 

Axial Coordination to Copper (II)—Peptide Complexes. Although inplane coordination dominates the thermodynamic, kinetic, and spectral properties of the Cu( II)-peptides, axial coordination also is important. While the carboxylate groups in Cu(H.3G4)2" and Cu(H 2GGhis)"... 

Substitution Kinetics of Copper(II)—Peptide Complexes. Three main reaction pathways have been found for the displacement of copper from peptide complexes—(1) proton transfer to the peptide group, (2) nucleo-... 

Copper (III)-Peptide Complexes. Molecular oxygen reacts with Cu(II)tetraglycine (G4) in neutral solution to produce a yellow species with an intense absorption band at 362 nm. As the oxygen in the solution is consumed, the amount of the yellow species decays (Figure 6). The uv-visible spectrum, molar absorptivity, dissociation kinetics in acid and in base, and the redox behavior of this yellow species are similar to those of Cunl(H.3G4)", which is generated by IrCl62 or by electrolytic oxidation of the corresponding Cu(II) complex. The peptide products after... 

Cu(I)-y-EC peptide complexes were isolated from the cultured cells of the fission yeast Schizosaccharomyces pombe when exposed to copper salts. Based on the similarity of the observed Cu(I) luminescence properties in the 600 nm region with those of Cu-MT (see Section 4), Cu -thiolate coordination was suggested. ... 

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