Complexation of copper(I) by thioamino acids. Implications for copper speciation in blood plasma

There is mounting evidence that Cu(I) is the most important oxidation state of copper in many physiological systems. Research into Cu(I)-thioamino acid complex formation serves not only to improve the chelation therapy for treating copper intoxication but may also provide a better understanding of many facets of normal copper metabolism. Formation constants for the ternary mixed ligand complexes of Cu(I) with cysteine (Cys), glutathione (GSH) and penicillamine (Pen) are reported here for the first time. Potentiometric titrations, using techniques specially developed for the stabilization of aqueous Cu(I), were performed at 25 degrees C in 1.00 M (Na)Cl. It was found that precipitation severely limits the experimentally accessible pH range and, consequently, the computer analysis of the binary metal-ligand systems; however, it is also found that this is less of a problem when two different ligands are present. This latter fact permitted better models of the binary systems to be developed. The formation constants of Cu(I)-thioamino acids determined in this work were used in an improved computer simulation of copper speciation in blood plasma which, for the first time, incorporates redox equilibria.