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Octadentate catecholamide ligands for Pu(IV) based on linear or preorganized molecular backbonesDepartment of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA
Department of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA
Department of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA
Department of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA
Department of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA
Department of Chemistry, University of California, Berkeley, Division of Chemical Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720, USA Nine new octadentate ligands based on cyclic, spermine (3,4,3-LI), desferrioxamine (DFO), or H-shaped tetrakis amine (penten) molecular backbones were prepared containing catecholamide (CAM), carboxycatecholamide (CAM(C)), or terephthalamide (TAM) chelating units. Mice were injected intravenously with 238Pu(IV) citrate, treated with 30 µmol kg-1 of a ligand by intraperitoneal injection at 1 h or by gastric intubation at 3 min, and Pu retention in tissues and Pu transfer to excreta were measured at 24 h. Given by injection, three soluble ligands composed of MeTAM (3,4,3-LIMeTAM, DFO-MeTAM, H(2,2)-MeTAM) reduced Pu retention in the body to 27- 28% of control compared with 32 and 37% of control obtained in mice similarly treated with 3,4,3-LICAM(C) or CaNa3-DTPA, respectively. The MeTAM ligands reduced Pu retention in the skeleton as much as an equimolar amount of CaNa 3-DTPA, while Pu retention in the liver (on average, 16% of control) was significantly less than was obtained with CaNa3-DTPA (35% of control). Given orally, H(2,2)-MeTAM reduced Pu retention in the whole body to 58% of control compared with reductions to 62 and 94% of control achieved with 3,4,3-LICAM(C) or CaNa3-DTPA, respectively. Penten is both partially preorganized for metal binding and spatially suitable for encapsulation of actinide(IV), and ligands with the penten backbone are easier and less costly to prepare than those based on spermine or DFO. The biological results confirmed that penten is a suitable as well as practical structural backbone for new octadentate ligands. In agreement with the great stability of the ferric complex with MeTAM, as determined in vitro, the small, simple, soluble penten- based octadentate ligand, H(2,2)-MeTAM, was shown to be, overall, the most effective catecholamide ligand for enhancing Pu excretion. Either combined in H(2,2)- MeTAM or separately, the penten backbone and the MeTAM chelating unit are potentially useful additions to the set of backbones and binding units of multidentate ligands identified as effective for in vivo chelation of the actinides.
Key Words: chelation therapy • octadentate catecholamide ligands • actinides
Human & Experimental Toxicology, Vol. 15, No. 4,
352-360 (1996) |
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