Stability of the Cu(II)-S Bond in Mercapto Amino Acid Complexes of [2,2^',2^''-Tris(dimethylamino)triethylamine]copper(II) and [Tris (2-pyridylmethyl) amine]copper(II

Comparative kinetic studies (pH 5.6-11.1) are reported for the oxidations of cysteine (cys-SH), cysteine methyl ester (cme-SH), penicillamine (pen-SH), and glutathione (glu-SH) coordinated to [2,2^',2^''-tris(dimethylamino)triethylamine]copper(II) (Cu-(Me₆tren)²⁺) and [tris(2-pyridylmethyl)amine]copper(II) (Cu(tmpa)²⁺). Relative stabilizations of (tmpa)Cu^II-SR species by factors of ca. 10⁴and 10 were found at low- and high-pH limits, respectively, suggesting that delocalization of thiolate sulfur negative charge over the π systems of aromatic nitrogen donor ligands contributes significantly to Cu(II)-S bond stability. Excluding the glutathione complexes, all of the Cu(tmpa)²⁺and Cu(Me₆tren)²⁺adducts exhibit reactivity decreases from intermediate to high pH, where S,N chelation by the amino acids is favored. A mechanism involving reductive elimination of sulfur to give Cu(I) and a thiyl radical is supported by this and other results. Oxidation rate constants of S,N-bonded cysteine and its methyl ester are not greatly different in complexes with both (tmpa)Cu^IIand (Me₆tren)Cu^II, but the reactivity of penicillamine is lower by more than 1 order of magnitude in both systems. This observation, coupled with unexpectedly slow ring closure to give (tmpa)Cu^II-S,N-pen, reflects geometric rearrangements in the first coordination sphere of copper required to accommodate the steric demands of the penicillamine β,β-dimethyl substituents. Redox decay rate constants of Cu(tmpa)²⁺adducts with S-cys, S-cme, and S-glu are remarkably small at low pH as well (<10^~3s^-1at 25 °C below pH 4) although S,O chelation does not contribute appreciably to the activation barrier.