Stopped-Flow Spectroscopic Studies on the Ligand-Exchange Reaction of Cu–(Glycine-Peptide) Complexes, Cu(H−iL), with Cysteine. Cu(II) Transport and Characterization of the Intermediate Ternary Complexes Cu(H−1L)(Cys−); L = Glycylglycine (i = 1), Triglycine (i = 2), Tetraglycine (i = 2 or 3), and Pentaglycine (i = 2 or 3)

Abstract

Abstract Cu(II) complexes of glycine-peptides, abbreviated as Cu(H−iL): L = glycylglycine, triglycine, tetraglycine, and pentaglycine (i = 1–3), react with cysteine to form ternary complexes, Cu(H−1L)(Cys−), as first intermediates. The spectral parameters of the ternary complexes, which were similar irrespective of the peptides, were as follows: λmax = 332 ± 1 nm (ε = 4250 ± 50 M−1 cm−1), g|| = 2.170 ± 0.005, g⊥ = 2.00 ± 0.05, and A|| = (2.05 ± 0.01) × 10−4 cm−1, indicating that the ternary complexes have identical coordination structures: the Cu(II) coordinates with the peptides via the nitrogens from the terminal amino and the neighboring deprotonated-amide group, and with cysteine via the amino nitrogen and the thiolate sulfur. Based on the absorbance-time curves, the concentrations of each Cu(II) and Cu(I) species during the reaction were calculated. The species distribution curve clearly visualized the pathway of the Cu(II) transport from Cu(H−iL) to Cu(Cys−)2 via Cu(H−1L)(Cys−). The rate of Cu(H−1L)(Cys−) formation, which was evaluated from the initial increase in the species distribution curve, depended on the coordination modes of the Cu(H−iL) complexes. Both the Cu(H−1L), involving N,N−,O−,O* donors, and the Cu(H−2L), involving N,N−,N−,O−* donors, rapidly formed Cu(H−1L)(Cys−) complexes, where the donors asterisked represent the fourth ligand in the Cu(H−iL) complexes. The second-order rate constant, k1+, was on the order of 106 M−1 s−1, or bigger. The Cu(H−3L), involving N,N−,N−,N−* donors, reacted relatively slowly; k1+ was on the order of 104 M−1 s−1. Those results indicate that the affinity of the Cu(II) for the fourth donor in Cu(H−iL) determines the rate of metal-transport.