Characteristics of chelate antidotes for acute Cu(II) intoxication

Abstract Twenty-four chelating agents have been screened experimentally to determine the structural features which are characteristic of the most effective of these as antidotes for acute Cu(II) intoxication in the mouse. When this data is combined with that obtained in previous studies on chronic copper intoxication, it can be seen that there are four structural classes of such antidotes whose pattern of donor atoms differ. In all four classes the complexes with Cu(II) are more stable than those with Ca(II) as required by Schubert's theory. The four classes are (a) vicinal dithiols; (b) the polyaminocarboxylates; (c) polyethyleneamines and their derivatives; and (d) compounds derived from the β-mercaptoethylamine structure. There is no obvious indication that the reduction of Cu(II) to Cu(I) is a necessary part of the manner in which these antidotes function. Of the various compounds examined, the best antidote appeared to be 2,3 dimercaptopropane sulfonate. The relative efficacy of the compounds examined suggests that there are probably a large number of other chelating agents which would show some promise as therapeutic agents under circumstances where it is desirable to enhance the excretion of copper.