Metal binding by pharmaceuticals. Part 5. Interaction of Cd(II), Ni(II) and Pb(II) with the intracellular hydrolysis products of the anti-tumour agent ICRF 159 and its inactive homologue ICRF 192.

Formation constants for the cadmium(II), nickel(II) and lead(II) complexes of DL-NN'-dicarboxamidomethyl-NN'-dicarboxymethyl-1,2-diaminopr opane (ICRF 198) and the 1,2-diaminobutane homologue (ICRF 226) have been measured potentiometrically at 37 degrees C and I = 150 mmol dm-3 [NaCl]. In all titrations a competing ligand, known to complex strongly with the metal ion, and having its formation constants predetermined, was employed. The constants are used in computer simulation models to assess the relative efficacy of the agents in mobilizing these metals from plasma proteins into low-molecular-weight complexes and the results are compared to those for known chelating agents. It is shown that the lead mobilizing potential of the agents is greater than either EDTA or D-penicillamine; they are, however, less adept in the removal of cadmium and nickel than other established agents.