Specific sequestering agents for the actinides: 10. Enhancement of 238Pu elimination from mice by poly(catechoylamide) ligands.
Macromolecules containing four sulfonated catecholy (2,3-dihydroxybenzoyl) groups are effective for decorporation of newly acquired Pu(IV). However, multiple injections in mice and single injections in dogs of 30 mumole/kg of 3,4,3-LICAM(S), 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 mumole/kg, intraperitoneally) 1 hr after an intravenous injection of 238Pu(IV) citrate, and mice were killed 24 hr after the Pu injection. Excreta and tissues were analyzed for Pu. (a) 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. (b) A mesitylene platform was substituted for the linear backbone. Net Pu excretion promoted by MECAM(S), a structurally less flexible trimer, was only 26%, and excretion was delayed. (c) A carboxyl substituent on the catechoyl groups reduced the acidity and hydrophilicity of the ligands. Tetrameric 3,4,3-LICAM(C) promoted 63% net Pu excretion, and one-third of that was fecal. The Pu contents of liver and skeleton were 33 and 44% of their respective 1-hr control values--compared to 51 and 44%, respectively, for CaNa3-DTPA. Mice given 30 mumole/kg of 3,4,3-LICAM(C) 20 times in 4 weeks showed no ill effects. (d) Large N-terminal alkane substituents added to 3,4,3-LICAM(C) increased ligand lipophilicity, hindered Pu chelation, and delayed excretion.
D000818:Animals; D002395:Catecholamines / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use; D003666:Decontamination; D005260:Female; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008024:Ligands / Q000627:therapeutic use; D051379:Mice; D011005:Plutonium / Q000378:metabolism*; D011108:Polymers / Q000627:therapeutic use; D013095:Spermidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002395:Catecholamines; D002614:Chelating Agents; D007502:Iron Chelating Agents; D008024:Ligands; D011108:Polymers; D011005:Plutonium; C030662:N,N',N''-tris(2,3-dihydroxy-5-sulfobenzoyl)-1,5,10-triazadecane; C034834:LICAM-C; D013095:Spermidine