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Rational Design of Sequestering Agents for Plutonium and Other Actinides

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Rational Design of Sequestering Agents for Plutonium and Other Actinides Chem. Rev. 2003, 103, 4207−4282 4207 Rational Design of Sequestering Agents for Plutonium and Other Actinides Anne E. V. Gorden, Jide Xu, and Kenneth N. Raymond* Department of Chemistry, University of California, Berkeley, California 94720 Patricia Durbin Chemical Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 Received December 23, 2002 Contents 6.6. Hydroxypyridinone (HOPO)-Based 4246 Plutonium-Sequestering Agents 1. Introduction 4208 6.7. Mixed Ligands 4249 2. Background 4209 6.8. Orally Effective HOPO Ligands 4251 2.1. Actinides in Applications 4209 6.9. Ligand Toxicity 4252 2.2. Behavior of Plutonium in Biological Systems 4209 6.10. Comparison of Efficacy for Pu Sequestration 4254 2.3. Chelation Therapy 4211 6.11. Ligands for Plutonium Removal from Bone 4255 2.4. Current Chelation Methods Using DTPA 4212 7. Thorium-Sequestering Agents 4256 3. Designing a Model System 4213 7.1. Thorium Coordination ChemistrysSimilarities 4256 3.1. Actinide Coordination Chemistry 4213 to Pu(IV) 3.1.1. Characteristic Features 4213 7.2. Structural Characterization as Model for the 4256 3.1.2. Lanthanides as Models for Actinides 4215 Pu(IV) System 3.2. Requirements for an Effective Sequestering 4216 7.3. Decorporation of Thorium 4259 Agent 8. Americium-Sequestering Agents 4260 3.3. Biological Means for Evaluation 4216 8.1. Americium Coordination Chemistry 4260 3.3.1. Initial Assessment 4216 8.2. Lanthanides(III) as Models for Am(III): Eu(III) 4261 3.3.2. Collaborative Studies 4218 and Lu(III) 4. A Biomimetic Approach toward 4219 8.3. Gd(III) Complexes as Models for Am(III) 4262 Actinide-Sequestering Agents 8.4. Multidentate Amino Acetic Acids for Am(III) 4262 4.1. Similarities between Fe(III) and Pu(IV) 4219 Chelation Therapy 4.2. Complexes with Naturally Occurring 4220 8.5. Multidentate CAM Ligands for Am(III) 4264 LigandssSiderophores Chelation Therapy 4.3. Design of Ligand Scaffolds 4221 8.6. Multidentate HOPO Ligands for Am(III) 4265 4.3.1. Chelating Groups in Siderophores 4221 Chelation Therapy 4.3.2. Multidentate Coordination Systems 4221 8.7. Ligands for Americium Removal from Bone 4265 4.3.3. Ligand Geometry and Denticity 4223 9. Uranyl Ion-Sequestering Agents 4266 5. Ligand Synthesis 4224 9.1. Uranium and Uranyl Coordination Chemistry 4266 5.1. Ligand Systems 4224 9.2. Uranium in Biological Systems 4268 5.2. Catecholamide (CAM) Ligands 4224 9.3. Depleted Uranium 4269 5.3. Terephthalamide (TAM) Ligands 4232 9.4. Uranyl Complexes with Multidentate CAM 4270 5.4. Hydroxypyridinone (HOPO) Ligands 4234 Ligands 5.5. Mixed Ligands 4236 9.5. Uranyl Complexes with Multidentate TAM 4270 Ligands 5.6. Sulfonamide Ligands 4237 9.6. Uranyl Complexes with Multidentate HOPO 4270 6. Plutonium-Sequestering Agents 4238 Ligands 6.1. Plutonium Coordination Chemistry 4238 9.7. Ligand Cocktails for Multiple Actinides 4271 6.2. Ce(IV) and Hf(IV) as Models for Pu(IV) 4239 10. Neptunium-Sequestering Agents 4273 6.3. Catecholamide (CAM)-Based 4241 10.1. Neptunium Coordination Chemistry 4273 Plutonium-Sequestering Agents 10.2. Neptunium under Physiological Conditions 4273 6.3.1. Cyclic Systems 4241 10.3. Neptunium Decorporation Using Multidentate 4274 6.3.2. Multidentate Linear Systems 4242 CAM Ligands 6.4. Biological Evaluation Leads to Improved 4242 10.4. Neptunium Decorporation Using Multidentate 4274 Ligand Systems HOPO Ligands 6.5. Terephthalamide (TAM)-Based Ligands 4246 11. Conclusions 4275 12. Acknowledgments 4276 * To whom correspondence should be addressed. Phone: (510) 642- 13. Abbreviations 4276 7219. Fax: (510) 486-5283. E-mail: [email protected]. 14. References 4277 10.1021/cr990114x CCC: $44.00 © 2003 American Chemical Society Published on Web 10/28/2003 4208 Chemical Reviews, 2003, Vol. 103, No. 11 Gorden et al. Anne E. V. Gorden was born in Kansas City, Missouri, and grew up in Professor Kenneth N. Raymond was born in 1942 in Astoria, Oregon. He the north Dallas area in Texas. A National Merit Scholar (1992) and attended Reed College, where he received a B.A. in 1964. His Ph.D. recipient of two General Electric Faculty for the Future Fellowships (1995, research at Northwestern University, under the direction of Professors 1996), she graduated from Emory University in Atlanta, Georgia, in 1996, Fred Basolo and James A. Ibers, concerned the synthesis and structure earning a B.S. in chemistry as well as completing a second major in of five-coordinate metal complexes. Upon completing his Ph.D., he began literature. She then returned to Texas, attending graduate school at the his faculty appointment at the University of California at Berkeley in 1967, University of Texas at Austin, where her thesis work, under the direction becoming Associate Professor in 1974 and Professor in 1978. His work of Professor Jonathan L. Sessler, concerned the design and synthesis of has been recognized with several awards, including the Ernest O. novel expanded porphyrins and oligopyrroles for selective ion coordination, Lawrence Award of the Department of Energy (1984), a Humboldt in a collaborative project with Los Alamos and Argonne National Research Award for Senior U.S. Scientists (1991), and the American Laboratories as a Seaborg Research Fellow (1999) and as a Seaborg Chemical Society Alfred Bader Award in Bioinorganic or Bioorganic Institute Research Fellow (2000−2002). In 1999 and 2000, she was Chemistry (1994). He has been an Alfred P. Sloan research fellow (1971− awarded two Delta Gamma Foundation Fellowships for Women in Science. 1973), a Miller research professor at the University of California (1977− After completing her dissertation in 2002, Dr. Gorden began a postdoctoral 1978, 1996) and Guggenheim fellow (1980−1981). He was elected to appointment at the University of California at Berkeley with Professor the National Academy of Sciences in 1997, and the American Academy Kenneth N. Raymond, investigating the structural and solution properties of Arts and Sciences in 2001. In addition to his academic appointment at of siderophore-based actinide-sequestering agents. the University of California, he is a cofounder of Lumiphore Inc., which utilizes new luminescent agents developed in his laboratory, and Faculty Senior Scientist and Interim Director of the Seaborg Center at Lawrence Berkeley National Laboratory. He is the author of 12 patents and approaching 400 research publications. shown to reduce acute radiation damage, chemical toxicity, and late radiation effects. The recent devel- opment of improved actinide-sequestering agents for potential use in chelation therapy has been based on a body of work in several areas of coordination chemistry. Key among these is the expansion of our fundamental understanding of the structural and solution (thermodynamics) coordination of the ac- tinides. This understanding allows lanthanide metal ions to be used as suitable models for the actinides. Jide Xu was born in China. He earned the equivalent of a B.S. in chemistry Described in this work is an overview of an approach in 1964 at Wannan University. After a brief period in agriculture in Anhui, toward the design and optimization of actinide- China (1964−1967), he worked for Anhui Chizhou Chemical Fertilizer sequestering agents. Factory in Anhui, China (1967−1980). After this time away from academics, he returned to Anhui University as a student and lecturer (1980−1986), This rational approach for the design of preorga- completing the equivalent of a Ph.D. in 1986. At that time, he was nized multidentate sequestering agents for actinides appointed an Associate Professor and Advisor to Graduate Students at was inspired by siderophores, the naturally occurring Anhui University, and for his work there he was recognized with an microbial iron(III)-sequestering agents. Biological Outstanding Teacher Collective Award (1989) and a Significant Achieve- ment Award of Anhui Science and Technology Commision (1989). He evaluation of the efficacy and toxicity of these ligands came to Berkeley first as a Visiting Scholar (1989−1992) and postdoctoral has provided comprehensive data for the ongoing research fellow (1990−1992), and is currently serving as Staff Scientist ligand optimization process. This has enabled the working with Professor Kenneth N. Raymond, involved in all aspects of development of a class of promising highly selective research and project development in his laboratories. agents for in vivo chelation of Pu(IV). In addition, several low-toxicity tetradentate linear ligands with a pentylene or diethyl ether backbones containing 1. Introduction catecholate or hydroxypyridinonate binding groups have been found to chelate other actinides and have Providing effective chelation therapy in response been identified as suitable agents for in vivo chelation to internal human actinide contamination has been of Am(III), Np(IV/V), or U(VI). Rational Design of Sequestering Agents for Actinides Chemical Reviews, 2003, Vol. 103, No. 11 4209 to actinides. Of these, plutonium (Pu) and uranium (U) are the elements most likely to be encountered. Plutonium has been manufactured through the ir- radiation of nuclear fuel to be isolated for material of a grade suitable for military use in weapons and space exploration applications, but in civilian energy production applications, plutonium is generated as a byproduct of systems that are based primarily on uranium fission.4 Today, with close to one-third of the world’s electrical power supply produced using nuclear sources,5 the overall amount of spent nuclear fuels generated each year is in the range of 9000- 10000 tons.4 This yearly quantity of spent fuel contains about 75 tons of Pu.4 The total amounts of plutonium produced from power reactors accumu- Patricia W. Durbin was born in Oakland, California. She received both lated globally is an estimated 7000 metric tons her B.S. in chemistry (1948) and her Ph.D. in biophysics (1953) from the worldwide, most of which is dilute and contained in University of California at Berkeley.
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