THE SYNTHESIS, THERMODYNAMIC BEHAVIOR, AND BIOLOGICAL PROPERTIES OF METAL-ION-SPECIFIC SEQUESTERING AGENTS FOR IRON AND THE ACTINIDES
Enterobactin, a microbial iron-transport compound which is a hexadentate ligand via its three catechol groups, has been studied by potentiometric, spectrophotometric and electrochemical techniques. The proton-dependent stability constant for the ferric enterobactin complex has been determined spectrophotometrically by competition vs EDTA. At physiological pH, enterobactin is by far the most powerful iron chelating agent yet characterized. In a biomimetic approach to the design and synthesis of ferric-ion-specific sequestering agents that could prove to be new therapeutic agents for iron mobilization in man, several structural analogs of enterobactin have been chosen as target compounds. Because of the large number of chemical and biological similarities of plutonium(IV) with iron(III) a biomimetic approach has also been taken in the synthesis of a new class of actinide-specific sequestering agents which incorporate four catechol groups. In general both the iron and actinide sequestering agents are derivatives of 2,3-dihydroxybenzoic acid or the 5-sulfo 2,3-dihydroxybenzoic acid derivatives. Both MECAM [1,3,5-N,N{prime},N{double_prime}-tris(2,3-dihydroxybenzoyl)triamino-methylbenzene] and 3,4-LICAMS [1,5,10-N,N{prime},N{double_prime}-tris(5-sulfo-2,3-dihydroxybenzoyl)triazadecane] have been found to remove iron from the human iron transport protein transferrin. In fact, all of the synthetic tricatecholate ligands rapidly remove iron from human transferrin - in marked contrast to the trihydroxamate ligands such as desferrioxamine B (the most commonly used drug for iron removal in man). The details of the kinetics of transferrin iron removal by 3,4-LICAMS have been investigated. In addition, the mode of coordination to ferric ion of enterobactin and analogous compounds has been investigated and the change in this coordination as a function of protonation of the metal-ligand complex characterized. Protonation of these compounds occurs through one-proton steps to give a salicylate mode of bonding in which the carbonyl oxygen of the 2,3-dihydroxybenzoyl group coordinates to the metal. The solution thermodynamics of the complexes formed between the tetra-catechol sequestering agents and thorium(IV) have been investigated in a preliminary fashion and these sequestering agents have undergone animal tests for their efficacy in decorporation of plutonium. Two of these compounds have been found to be far superior at low concentration to any of the sequestering agents presently used in actinide contamination treatment.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- Materials Sciences Division
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 1030593
- Report Number(s):
- LBL-10466; TRN: US201124%%340
- Resource Relation:
- Conference: American Chemical Society Meeting, Washington, D.C., September 10-11, 1979
- Country of Publication:
- United States
- Language:
- English
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