[In vitro uranyle affinity of per (3,6-anhydro-2-O-carboxyméthyle)-alpha-cyclodextrin and conditions required for in vivo application]

Abstract

Per (3.6-anhydro-2-O-carboxymethyle)- alpha-cyclodextrin ([1]) is a polydentate analog of EDTA, a well-known cation chelating reagent. [1] exhibits strong affinities in vitro for lanthanids, cobalt and also for uranyl cations. Hence, a 1:1 stoechiometry and a high affinity for uranyle (6<logK<7) is found in vitro. Moreover, [1] is not hemolytic and exhibits not lettral properties in mice (LD(50)=42mM). In vivo injection at supralethal amounts of uranyl complex of [1] prevents immediate death in mice while unable to protect against later death. Pharmacocinetic studies show that a dissociation of the complex occurs lead to the release of free uranyle. Other complexation assays using [1] grafted tissues show that chelating properties for lead and uranyle differ from thoses observed in vitro.