Therapeutic uses of copper-chelating agents.

Equilibrium analysis of a model system for the in vivo reactions between penicillamine and copper (I), the penicillamine--glutathione--Cu(I) system, indicates that in a certain concentration range the therapeutic use of penicillamine will not disturb the normal Cu(I) metabolism. The equilibrium data required for this analysis were obtained by e.m.f. titrations on the Cu(I)-glutathione (H3A) and on the Cu(I)-penicillamine (H2A) systems at 25 degree C, in 0.5 M NaClO4 medium, using glass and copper amalgam electrodes; the data were analysed 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, from in both systems; in addition, the polynuclear Cu5A4(3-) 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.