Specific Sequestering Agents for the Actinides: 10. Enhancement of 238 Pu Elimination from Mice by Poly(catechoylamide) Ligands

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Abstract
Macromolecules containing 4 sulfonated catechoyl (2,3-dihydroxybenzoyl) groups are effective for decorporation of newly acquired [carcinogen] Pu(IV). Multiple injections in mice and single injections in dogs of 30 .mu.mol/kg of 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetraacetetradecane, tetrasodium salt], the most effective sulfonated poly(catechoylamide) ligand, indicated that it would be toxic, so the ligand structure was modified. Each ligand was injected into mice (30 .mu.mol/kg, i.p.) 1 h after an i.v. injection of 238Pu(IV) citrate, and mice were killed 24 h after the Pu injection. Excreta and tissues were analyzed for Pu. The number of catechoyl groups per molecule was reduced to suppress affinity for Fe(III). Net excretion (treated - control) of 55% of the injected Pu was promoted by tetrameric 3,4,3-LICAM(S), 51% by trimeric 3,4-LICAM(S), 22% by dimeric 2-LICAM(S) and 7.4% by the monomer, Tiron. A mesitylene platform was substituted for the linear backbone. Net Pu excretion promoted by MECAM(S) [N,N'',N"-tris(2,3-dihydroxy-5-sulfobenzoyl)-1,3,5-tris(aminomethyl)benzene, tripotassium salt], a structurally less flexible trimer, was only 26%, and excretion was delayed. A carboxyl substituent on the catechoyl groups reduced the acidity and hydrophilicity of the ligands. Tetrameric 3,4,3-LiCAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)tetraazatetradecane, tetrasodium salt] promoted 63% net Pu excretion, and 1/3 of that was fecal. The Pu contents of liver and skeleton were 33 and 44% of their respective 1-h control values.sbd.compared to 51 and 44%, respectively, for CaNa3-DTPA. Mice given 30 .mu.mol/kg of 3,4,3-LICAM(C) 20 times in 4 wk showed no ill effects. Large N-terminal alkane substitutents added to 3,4,3-LICAM(C) increased ligand lipophilicity, hindered Pu chelation and delayed excretion.

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