FERRIC ION SEQUESTERING AGENTS .2. KINETICS AND MECHANISM OF IRON REMOVAL FROM TRANSFERRIN BY ENTEROBACTIN AND SYNTHETIC TRICATECHOLS

The apparent first-order rate constants for iron removal from transferrin by the synthetic sequesteringagents 1, 5, 10-N, Nʹ,Nʺ-tris(5-sulfo-2, 3-dihydroxybenzoyl)triazadecane (3, 4-LiCAMS), 1, 3, 5-N, Nʹ,Nʺ-tris(2, 3-dihydroxybenzoyl)aminomethylbenzene (MECAM), and the natural siderophore enterobactin (ent) have been determined at 25 °C. One of these compounds, 3, 4-LICAMS, was examined in detail, and the mechanism of its removal of iron from transferrin elucidated. The 3, 4-LICAMS ligand is observed to form a complex with transferrin prior to iron removal. The stability constant of this complex and the first-order rate constant for its dissociation to ferric LICAMS and apotransferrin are Keq = 4.1 (6) X 102M-1 and k2 = 0.066 (4) min-1, respectively. These results indicate that these catecholate ligands are both kinetically and thermodynamically capable of iron removal from transferrin at physiologically accessible concentrations. In contrast, the hydroxamate-based sequestering agents are kinetically hindered in this reaction. The implications of these results with respect to the possible use of these compounds as drugs in the treatment of iron overload syndromes are discussed. © 1979, American Chemical Society. All rights reserved.