Rational Ligand Design for U(VI) and Pu(IV)* by Géza Szigethy B.A. (Princeton University), 2004 A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Chemistry in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Kenneth N. Raymond, Chair Professor Richard A. Andersen Professor Garrison Sposito Fall 2009 * This research and the ALS are supported by the Director, Office of Science, Office of Basic Energy Sciences (OBES), and the OBES Division of Chemical Sciences, Geosciences, and Biosciences of the U.S. Department of Energy at LBNL under Contract No. DE-AC02- 05CH11231. Rational Ligand Design for U(VI) and Pu(IV) by Géza Szigethy B.A. (Princeton University), 2004 A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Chemistry in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Kenneth N. Raymond, Chair Professor Richard A. Andersen Professor Garrison Sposito Fall 2009 Rational Ligand Design for U(VI) and Pu(IV) Copyright © 2009 Géza Szigethy Abstract Rational Ligand Design for U(VI) and Pu(IV) by Géza Szigethy Doctor of Philosophy in Chemistry University of California, Berkeley Professor Kenneth N. Raymond, Chair Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly- bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) 2+ dioxo dication (uranyl, UO2 ). The goal is to utilize rational ligand design to develop 1 ligands that exhibit shape selectivity towards linear dioxo cations and provides thetIDodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTP A, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-bidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these ligands exhibited increased uranyl affinity compared to bis-Me-3,2-HOPO ligands. This result is due in part to their increased denticity, but is primarily the result of the presence of the TAM moiety. In an effort to explore the relatively unexplored coordination chemistry of Pu(IV) with bidentate moieties, a series of Pu(IV) complexes were also crystallized using bidentate hydroxypyridinone and hydroxypyrone ligands. The geometries of these complexes are compared to that of the analogous Ce(IV) complexes. While in some cases these showed the expected structural similarities, some ligand systems led to significant coordination changes. A series of crystal structure analyses with Ce(IV) indicated that these differences are most likely the result of crystallization condition differences and solvent inclusion effects. 2 Acknowledgements First and foremost I would like to thank my advisor, Professor Ken Raymond. Throughout my studies he has been supportive of the pursuit of my own interests as they apply to the research in his group; this has been the case from the first time we met and I requested to work on the subject of this dissertation. As my research progressed, he allowed those interests to naturally lead me along various avenues of investigation as he encouraged me to become a more well-rounded scientist and fill in the gaps my approach naturally created. I am also immensely grateful for his support of my life outside of the lab, helping to ensure that I was not just well-rounded in science, but in life as well. I have by no means worked in a vacuum these past five years, and I have been assisted and encouraged by a large number of people in various fields without whom this research project would not have progressed as it has. Firstly, I want to thank Dr. David Shuh of Lawrence Berkeley National Labs (LBNL). He has been a constant source of encouragement and significant assistance in the workings of LBNL and has ensured that much of my work with Pu(IV) and U(VI) at the National Lab proceeded with acceptable speed and efficiency. He, too, has supported my life outside the lab, which is of course also greatly appreciated. Throughout my time in the Raymond group I have found myself very interested in X- ray crystallography, in which I have been assisted by several experts: Drs. Fred Hollander, Allen Oliver, and Antonio DiPasquale of UC Berkeley and Dr. Simon Teat of the Advanced Light Source at LBNL. These four, in addition to Ken, have taught me to evaluate, collect, and refine x-ray crystallographic data and have encouraged my constant development in the subject, for which I thank them. i Many people within the Raymond group have also been of great assistance to me, starting with Prof. Anne Gorden and Dr. John Gorden, who introduced me to the Raymond group, its research, and lab practice in general. They also introduced me to working with radioactive isotopes and instructed me on how to do so safely. Many thanks are deserved by Dr. Jide Xu, whose synthetic expertise I have inquired upon many times, and who has never been too busy to knock about crazy synthesis ideas and suggest ways to actually make them possible. I greatly appreciate the assistance of Dr. Rebecca Abergel, Trisha Hoette, and Dr. Brandi Schottel for passing on their combined wisdom on solution titrations and their patience with my many questions and requests for help interpreting results. My time in the Raymond group has been made much more enjoyable due to the company of many of my lab mates. Dr. Mike Pluth and Trisha Hoette have been great company and provided many a sounding board for a variety of subjects. Drs. Anthony D’Aleo, Evan Moore, and Michael Seitz have also shared their friendship as well as their knowledge with me. I could not list everyone else without forgetting many people, so I will settle with saying that I appreciate my interactions with all my labmates and groupmates, and I thank them for their support and friendship throughout my time in Berkeley. I also want to thank my family for their support of my efforts in graduate school. And finally I want to thank my wife Dora for all her support throughout my doctoral research. She has been incredibly patient and phenomenal in helping us survive the distance over these five years. She has sacrificed much in support of me, my efforts here, and our marriage, for which I am eternally grateful. − THANK YOU ALL! ii Table of Contents Acknowledgements ………………………………………………………………………. i Table of Contents ……………………………………………………………………….. iii List of Figures, Tables, and Schemes …………………………………………………... vii Chapter 1: Introduction………………………………………………………………… 1 1.1 Nuclear Waste ………………………………………………………………………... 1 1.2 Treatment of Radioactive Waste: The Selectivity Problem ………………………….. 4 1.3 Actinides in Biology; Chelation Therapy ……………………………………………. 9 1.4 Rational Ligand Design: Siderophore-Inspired Sequestering Agents ……………… 12 2+ 1.5 Ligand Design for the Uranyl Cation, UO2 ……………………….………………. 15 1.6 Ligand Design for Pu(IV) ….……..……………………….………………………... 21 1.7 Focus of the Current Study ..……………………………….……………………….. 23 1.8 References …………….….……………………………….………………………… 26 Chapter 2: Design, Structure, and Solution Thermodynamics of UO2(Bis-Me-3,2- HOPO) Complexes ……………………………………………………………. 32 2.1 Introduction ..………………………………………………………………………... 32 2.2 Results and Discussion ………………………………………………………………35 2.2.1 Tetradentate Ligand Design and Synthesis ……………………………….. 35 2+ 2.2.2 Synthesis and Structural Comparison of UO2 Complexes………………. 38 2.2.3 Soluble Tetradentate Ligand Design and Synthesis ………………………. 55 2+ 2.2.4 Ligand Substitution Effects on UO2 Complexes ………………………... 62 iii 2.2.5 Solution Thermodynamics ………………………………………………... 73 2.2.6 Substituted m-Xylene-Me-3,2-HOPO Ligands: Synthesis and Structure … 85 2.3 Conclusions and Future Directions………………………………………………….. 92 2.4 Experimental ………………………………………………………………………... 94 2.4.1 Synthesis of Backbone Diamines ………………………………………….94 2.4.2 Synthesis of Benzyl-Protected bis-Me-3,2-HOPO Ligands ……………...104 2.4.3 Benzyl-Deprotection of bis-Me-3,2-HOPO Ligands ……………………. 114 2+ 2.4.4 Synthesis/Crystallization Techniques for UO2 Complexes …………….122 2.4.5 X-ray Diffraction Data Collection ………………………………………. 128 2.4.6 Titrations