Chemistry of copper peptide complexes: Alkoxide coordination in copper(II) and copper(III) peptide complexes, and base decomposition of copper(III) peptide complexes

Lihua Wang, Purdue University

Abstract

In the Cu(II) and Cu(III) complexes of peptides with a hydroxyl group in the third residue, the alkoxide group can bind to the copper. The pK$\sb{\rm a}$ values of the hydroxyl group deprotonation depend on the nature of the group it displaces with relative magnitudes of carboxylate group $>$ peptide oxygen $>$ water. Alkoxide is a stronger donor than carboxylate, peptide oxygen, and water, but a weaker donor than deprotonated peptide nitrogen. The coordination of the alkoxide group greatly increases the stability of Cu(III) complexes relative to the Cu(II) complexes. At physiological pH, a hydroxyl group in the third residue cannot deprotonate and bind to Cu(II), but it can deprotonate and bind to Cu(III). The higher the reduction potential of Cu(III,II) couple, the faster the Cu(III) complex decomposes. The pseudo-first-order base decomposition (pH 11.0) rate constants of Cu(III)tetrapeptides and Cu(III)tripeptide amides that contain glycyl(G), alanyl(A), and $\alpha$-aminoisobutyryl(Aib) residues only depend on the reduction potential of the Cu(III,II) couple (E$\sp{\rm o})$. The E$\sp{\rm o}$ value depends on the number of $\alpha$-methyl substituents on the peptide residues. The more $\alpha$-substituents, the lower the E$\sp{\rm o}$, and the slower the Cu(III) complex decomposes. The rate constant of Cu(III)Aib$\sb3$a is smaller than that predicted from its E$\sp{\rm o}$ value, which suggests that $\alpha$-hydrogens are important in the mechanism of the Cu(III) complexes of other peptides. In the base decomposition of Cu(III)G$\sb4$ and Cu(III)G$\sb2$AG, the peptide ligand is oxidized by more than two electrons and the oxidations occur at all the peptide residues. Several types of ligand oxidation are observed, which include $\alpha$-amidation, oxidative decarboxylation, and probably amine or peptide nitrogen hydroxylation and carbon-carbon bond fragmentation other than decarboxylation.

Degree

Ph.D.

Advisors

Margerum, Purdue University.

Subject Area

Chemistry

COinS