OCTADENTATE CATECHOLAMIDE LIGANDS FOR PU(IV) BASED ON LINEAR OR PREORGANIZED MOLECULAR BACKBONES

Citation
Pw. Durbin et al., OCTADENTATE CATECHOLAMIDE LIGANDS FOR PU(IV) BASED ON LINEAR OR PREORGANIZED MOLECULAR BACKBONES, Human & experimental toxicology, 15(4), 1996, pp. 352-360
Citations number
45
Categorie Soggetti
Toxicology
ISSN journal
09603271
Volume
15
Issue
4
Year of publication
1996
Pages
352 - 360
Database
ISI
SICI code
0960-3271(1996)15:4<352:OCLFPB>2.0.ZU;2-O
Abstract
Nine new octadentate ligands based on cyclic, spermine (3,4,3-LI), des ferrioxamine (DFO), or H-shaped tetrakisamine (penten) molecular backb ones were prepared containing catecholamide (CAM), carboxycatecholamid e (CAM(C)), or terephthalamide (TAM) chelating units. Mice were inject ed intravenously with Pu-238(IV) citrate, treated with 30 mu mol kg(-1 ) of a ligand by intraperitoneal injection at 1 h or by gastric intuba tion at 3 min, and Pu retention in tissues and Pu transfer to excreta were measured at 24 h. Given by injection, three soluble ligands compo sed of MeTAM (3,4,3-LIMeTAM, DFO-MeTAM, H(2,2)-MeTAM) reduced Pu reten tion in the body to 27-28% of control compared with 32 and 37% of cont rol obtained in mice similarly treated with 3,4,3-LICAM(C) or CaNa3-DT PA, respectively. The MeTAM ligands reduced Pu retention in the skelet on as much as an equimolar amount of CaNa3-DTPA, while Pu retention in the liver (on average, 16% of control) was significantly less than wa s obtained with CaNa3-DTPA (35% of control). Given orally, H(2,Z)-MeTA M reduced Pu retention in the whole body to 58% of control compared wi th reductions to 62 and 94% of control achieved with 3,4,3-LICAM(C) or CaNa3-DTPA, respectively. Penten is both partially preorganized for m etal binding and spatially suitable for encapsulation of actinide(IV), and ligands with the penten backbone are easier and less costly to pr epare than those based on spermine or DFO. The biological results conf irmed that penten is a suitable as well as practical structural backbo ne for new octadentate ligands. In agreement with the great stability of the ferric complex with MeTAM, as determined in vitro, the small, s imple, soluble penten-based octadentate ligand, H(2,2)-MeTAM, was show n to be, overall, the most effective catecholamide ligand for enhancin g Pu excretion. Either combined in H(2,2)MeTAM or separately, the pent en backbone and the MeTAM chelating unit are potentially useful additi ons to the set of backbones and binding units of multidentate ligands identified as effective for in vivo chelation of the actinides.