Copper(I) complexes of penicillamine and glutathione.

Equilibrium analysis of a model system for the in vivo reactions between penicillamine and Cu(I), the penicillamine-glutathione-Cu(I) system, indicates that in a certain concentration range the use of penicillamine as a drug will not disturb the normal Cu(I) metabolism. The equilibrium data required for this analysis were obtained by emf titrations on the Cu(I)-glutathione (H3A) and the Cu(I)-pencillamine (H2A) systems at 25 degrees C. in 0.5 M NaClO4 medium, using glass and copper amalgam electrodes; the data were analyzed first by various graphical methods and then by a general least squares computer program. The results show that mononuclear Cu(I) species Cu(HA)2 form in both systems with stability constants log beta 122 of 38.8 (glutathione) and 39.18 (penicillamine); in addition, the polynuclear Cu5A43- species forms in the penicillamine system and the mononuclear CuHA- species might form in the glutathione system. The results are discussed in relation to the therapeutic use of penicillamine as well as in relation to the toxic action of copper on living cells.