Evaluation of Speciation Technology - OECD Nuclear Energy Agency

Introduction
The actinide elements Pu, Np, Am and U are important industrial materials and consequent
environmental hazards [1,2]. Both 239 Pu and 235 U are nuclear fuels as well as constituents of nuclear
weapons. The heavier actinides are abundant in irradiated nuclear fuel and wastes from fuel
fabrication, fuel processing and weapons production. Weapons testing, accidents, and poor waste
disposal practices have contaminated the environment. It seems likely that future accident and
environmental contamination will have to be dealt with.
The biological and environmental behaviours of the actinides are reasonably well understood [1].
All of these hard cations form complexes with bioligands. Following human inhalation, ingestion, or
deposition in wounds, the absorbed actinides circulate, bound in various degrees to the Fe
transportation protein (transferring, TF). This protein binding severely inhibits renal excretion
(particularly of Pu and Am) and favours deposition in tissues. Cells and structures that die or are
remodelled release their actinide to the circulation, and some released Np and U and most of the
released Am and Pu re-deposit at new sites within the body.
Aggressive protracted chelation therapy reduces actinide concentrations and radiation doses in the
target tissues, thereby reducing chemical and radiation damage and tumour risk [1,2]. Therefore
chelating agents that form stable excretable actinide complexes are the only practical treatment for
reducing internal actinide contamination. The calcium and zinc salts of diethylenetriaminepentaacetate
(CaNa3DTPA, ZnNa3DTPA) have been the only clinically accepted agents for treating internal
actinide contamination. DTPA is a non-specific metal chelating agent, which does not solubilise Pu
hydroxides or remove Pu from bone mineral. It is not orally effective. It is ineffective for in vivo
chelation of Np and U. Therefore, development of ligands that are better chelating agents for actinides
than DTPA remains an important component of radiation protection research.
Design strategy
The actinide ions have large charge to radius ratios, they belong to the group of “hard” cations
and prefer hard electron donors such as oxygen. The co-ordination properties of Fe(III) are similar to
those of the actinides, especially Pu(IV), and that metal binding units with great affinity for Fe(III)
also form stable Pu(IV) complexes, as is shown by the incorporation of Pu and Am into mammalian
iron transport and storage systems. Siderophores are naturally occurring Fe(III) sequestering agents
produced by plants and bacteria in order to obtain growth limiting iron. The siderophores have very
high affinities for Fe(III). Enterobactin, a siderophore secreted by E. coli, has three catecholamide
binding sub units attached to a macrocyclic trilactone backbone, is pre-organised for binding iron [2].
It has the highest formation constant known for ferric ion, Kf = 10 49 . The binding sub units found in
siderophores are catecholates, hydroxamates or hydroxypyridinonates (HOPOs), the structures of their
protypes are shown below:
Catechol hydroxamic acid 1.2-HOPO 3.2-HOPO 3.4-HOPO
OH
R 1
O
OH
O
OH
OH
R 2
N
OH
N
OH
O
N
H
O
N
H
These binding sub units tend to be extremely specific for Fe(III) as well as Pu(IV). Therefore, we
have chosen a biomimetic approach for the design of sequestering agents for the actinide ions.
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