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Burbankk0814.Pdf (7.022Mb) A MOLECULAR BASIS FOR URANIUM TOXICITY by Katherine Ann Burbank A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry MONTANA STATE UNIVERSITY Bozeman, Montana May 2014 ©COPYRIGHT by Katherine Ann Burbank 2014 All Rights Reserved ii ACKNOWLEDGEMENTS I would like to start by thanking my two wonderful research advisors, Professor Brent Peyton and Professor Robert Walker. Professor Peyton saved me from an unfortunate situation and provided me with insight and expertise in the field of environmental uranium contamination and toxicity. Additionally, Professor Peyton’s mentorship and advice over this past year allowed me to mature as a scientist and gave me the confidence that I needed to complete my dissertation. I am also grateful for the 2+ work that Dr. Micheal VanEngelen did on describing the interaction of PQQ with UO2 under the mentorship of Professor Peyton. His contibutions to the PQQ toxicity mechanism are what made this work possible. In my first year of graduate school, I had the pleasure of learning both Thermodynamics and Quantum Mechanics from Professor Walker. His knowledge and expertise in the subjects are to be admired. I thank him for not only laying out the foundation for my work in physical chemistry, but for his continued support and guidance throughout my time at Montana State University. Lastly, I am thankful for the support and camaraderie from my former Szilagyi lab memembers, the chemistry department, and my family. Matt Queen, Brad Towey, Rhonda Barton, Mike Vance, Professor Mary Cloninger, Doreen Brown, Professor Valerie Copié, Professor Robin Gerlach, Paul Jordan, Russ Burbank, Mr. Bowie, and David Hoffman, I couldn’t have done it without you! And especially to my mother, Marguerite Burbank, I love you and miss you everyday. I wish I could share this with you. iii TABLE OF CONTENTS 1. INTRODUCTION ...........................................................................................................1 Uranium ...........................................................................................................................2 Environmental Contamination .................................................................................2 Coordination Chemistry ...........................................................................................3 Toxicity Mechanisms ...............................................................................................5 2+ UO2 Interaction with Pyrroloquinoline Quinone (PQQ) .......................................7 Biotic Ligand Model ....................................................................................8 PQQ Dependent Bacterial Dehydrogenase ..................................................9 Density Functional Theory ............................................................................................14 Exchange Functionals ............................................................................................17 Correlation Functionals ..........................................................................................17 Basis Sets ...............................................................................................................18 Development of Computational Models ................................................................20 Research Directions .......................................................................................................22 2. DEVELOPMENT OF A COMPUATIONAL MODEL TO DESCRIBE U(VI) AND PYRROLOQUINOLINE QUINONE INTERACTIONS .......................................................................................24 Contribution of Authors and Co-Authors ......................................................................24 Manuscript Information Page ........................................................................................25 Abstract ..........................................................................................................................26 Introduction ....................................................................................................................27 Computational Details ...................................................................................................30 Results and Discussion ..................................................................................................32 Modeling the PQQ Cofactor ..................................................................................32 Geometric Structure .......................................................................................33 Protonation Constant (pKa) ............................................................................36 Redox Potential ..............................................................................................40 Electronic Structure .......................................................................................41 2+ Modeling the UO2 Cation ...................................................................................43 Geometric Structure .......................................................................................44 Protonation Constant ......................................................................................47 Redox Potential ..............................................................................................49 Electronic Structure .......................................................................................50 3- 2+ Modeling PQQ /UO2 Interactions ..............................................................................52 Energetics .......................................................................................................53 Electronic Structure .......................................................................................56 Conclusions ....................................................................................................................60 References ......................................................................................................................62 iv TABLE OF CONTENTS CONTINUED 2+ 2+ 3. THE EFFECTS OF CA DISPLACEMENT BU UO2 ON THE BIOLOGICAL FUNCTION OF METHANOL DEHYDROGENASE .............................................................................67 Contribution of Authors and Co-Authors ......................................................................67 Manuscript Information Page ........................................................................................68 Abstract ..........................................................................................................................69 Introduction ....................................................................................................................70 Computational Details ...................................................................................................75 Results and Analysis ......................................................................................................76 The Addition-Elimination Mechanism ..................................................................76 The Modified Addition-Elimination Mechanism ..................................................81 The Hydride Transfer Mechanism .........................................................................84 2+ The Modified Addition-Elimination Reaction with UO2 Present .......................87 Discussion ..............................................................................................................92 References ......................................................................................................................96 4. A MOLECULAR BASIS FOR METAL TOXICITY BY URANIUM(VI) IN PQQ DEPENDENT BACTERIAL DEHYDROGENASE .............................................................................99 Contribution of Authors and Co-Authors ......................................................................99 Manuscript Information Page ......................................................................................100 Abstract ........................................................................................................................101 Introduction ..................................................................................................................102 Experimental and Theoretical Methods .......................................................................105 Chemicals .............................................................................................................105 Spectrophotometry ...............................................................................................106 Stability Constants ...............................................................................................106 Mass Spectrometry...............................................................................................108 Computational Details .........................................................................................108 Results and Discussion ................................................................................................109 2+ 2+ UO2 Displacement of Ca on PQQ and DPA ..................................................109 2+ 2+ UO2 Displacement of Ca on DPA ..................................................................112 2+ UO2 Displacement of other metals on DPA ......................................................115 2+ ESI-Mass Spectrometry Investigation
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