Hyperpolarization with Parahydrogen in NMR Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen University zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigte Dissertation vorgelegt von Sören Lehmkuhl, M.Sc. aus Göttingen Berichter: Prof. Dr. rer. nat. Dr. h.c. Bernhard Blümich Prof. Dr. rer. nat. Stephan Appelt Prof. Dr. rer. nat. Thomas Theis Tag der mündlichen Prüfung: 19.02.2019 Diese Dissertation ist auf den Internetseiten der Universitätsbibliothek verfügbar. 2 Hyperpolarization with Parahydrogen in NMR Hyperpolarization with Parahydrogen in NMR Parts of this thesis have already been published. My contributions are written in italic: Suefke, M., Lehmkuhl, S., Liebisch, A., Blümich, B., Appelt, S., 2017. Para-hydrogen raser delivers sub-millihertz resolution in nuclear magnetic resonance. Nature Physics 13, 568-572. All authors wrote the manuscript. I designed, optimized and prepared all SABRE samples to surpass the RASER threshold and selected appropriate substrates. The experiments were conducted together with Martin Süfke, Alexander Liebisch and Stephan Appelt. I discussed the experimental results and contributed to the developed model for the spin order transfer mechanism. Lehmkuhl, S., Emondts, M., Schubert, L., Spannring, P., Klankermayer, J., Blümich, B., Schleker, P.P.M., 2017. Hyperpolarizing Water with Parahydrogen. Chemphyschem 18, 2426-2429. I wrote the original draft of the manuscript until Meike Emondts and Phillip Schleker revised it. As all authors, I contributed to the final version of the publication. I initiated the project, prepared the SABRE samples, conducted the experiments and analyzed the experimental results together with Lukas Schubert. Lehmkuhl, S., Wiese, M., Schubert, L., Held, M., Küppers, M., Wessling, M., Blümich, B., 2018. Continuous hyperpolarization with parahydrogen in a membrane reactor. J Magn Reson 291, 8-13. I wrote the manuscript and all authors contributed to its final version. Martin Wiese and I designed the experimental setup and supervised the experiments. I analyzed the experimental results together with Lukas Schubert. In Preparation: Appelt, S., Kentner, A., Lehmkuhl, S., Blümich, B., From LASER physics to the para-hydrogen pumped RASER, invited for Prog Nucl Magn Reson Spectrosc. For this manuscript, I supported Stephan Appelt to write and proofread the manuscript, designed a system, which enabled giant RASER pulses, prepared all SABRE samples and conducted the experiments together with Arne Kentner and Stephan Appelt. Hyperpolarization with Parahydrogen in NMR 3 Acknowledgement A large number of people have supported and contributed to this thesis in various ways. Here, I would like to acknowledge some of them. First of all, I would like to thank my doctorate supervisor Prof. Dr. Dr. h.c Bernhard Blümich, who entrusted me with the chance to work in his group. Despite being burdened by many other issues, he always took the time to discuss my research and allowed me to work on the topics I found most interesting and encouraged me to develop and follow my own ideas. Secondly, I would like to thank my co-supervisor Prof. Dr. Stephan Appelt, for the informal atmosphere and patience to discuss current scientific subjects concerning the RASER project and far beyond it. Thanks to all former and present colleagues at the ITMC of the RWTH Aachen University for the nice working atmosphere, enriching discussions and fruitful cooperation. Special thanks go several people: - to Dr. Markus Küppers, who always found time to listen and his administrative support. - to all my students Stefan Benders, Anna Friedrich, Bin Kang, Larissa Klass, Annette Nordhausen and Monica Spritzky for their great work and especially Lukas Schubert, who also supported the lab for more than a year. - to the chemical apprentice Alexander Eltester for good work in the lab - to Dr. Meike Emondts, Dr. Peter Spannring and Dr. Philipp Schleker for the collaboration on the water project, the latter additionally for his initial support on the Augustine project. - to Martin Süfke, Alexander Liebisch and Arne Kentner for the exciting mutual work on the raser project. - and finally to my colleague Martin Wiese from the AVT for the productive cooperation on the DGF project “Mikro-PHIP NMR”, which lead to “Continuous hyperpolarization with a membrane reactor”. Next, I would like to thank Prof. Dr. Simon Duckett who introduced the SABRE approach to me during my ERASMUS exchange as a master student at the University of York. This includes his working group, especially Dr. Marianna Fekete and Dr. Ryan Mewis who supervised me. Special thanks to my friend and colleague Patrick Offer for inspiring discussions, relaxing holidays for distraction when needed and the proofreading of this work. Further personal thanks are dedicated to all my friends, especially Jean-André Schramm and Andreas Schümmer, to help me sustain a healthy work-life balance. This also includes my friend Kathy Schmitz for hosting the reoccurring Sunday evening events and all those who contributed to them. Finally, I am grateful for the support and encouragement of my parents Carola and Frank throughout my whole duration of study and my brother Till, who was always there for me and proofread this work. 4 Hyperpolarization with Parahydrogen in NMR Table of contents Hyperpolarization with Parahydrogen in NMR ....................................................... 2 Acknowledgement................................................................................................................................ 3 Table of contents ................................................................................................................................... 4 List of figures ........................................................................................................................................... 7 List of tables ...........................................................................................................................................10 Abbreviations ........................................................................................................................................11 Variables .................................................................................................................................................15 Important symbols and constants .................................................................................................17 1 Introduction .................................................................................................. 18 1.1 Sensitivity in NMR ..................................................................................................................20 1.2 Hyperpolarization in low field NMR .................................................................................23 2 Theory: Parahydrogen based hyperpolarization in NMR .......................... 25 2.1 What is parahydrogen? ........................................................................................................26 2.2 Parahydrogen induced polarization (PHIP) ...................................................................29 2.2.1 The catalytic cycle ..................................................................................................................30 2.2.2 Heterogeneous PHIP catalysts ...........................................................................................32 2.2.3 Pairwise replacement and other exchange mechanisms .........................................32 2.3 Signal amplification by reversible exchange (SABRE) ...............................................34 2.3.1 The catalytic cycle ..................................................................................................................35 2.3.2 Substrate classes and applications...................................................................................38 2.4 Efficiency in hyperpolarization experiments ................................................................39 2.5 Spin order transfer mechanisms in PHIP experiments ..............................................41 2.5.1 Level anti crossings (LACs) ..................................................................................................42 2.5.2 The role of LACs in SABRE experiments ..........................................................................43 3 Devices, synthesis and experimental procedures ...................................... 48 3.1 Devices.......................................................................................................................................48 3.1.1 Magnets as detection fields ................................................................................................49 3.1.2 Magnets for polarization transfer fields .........................................................................51 3.1.3 Parahydrogen generators ...................................................................................................51 3.2 Synthesis ...................................................................................................................................52 3.2.1 Synthesis of [IrCl(COD)(IMes)] ............................................................................................52 3.2.2 Synthesis of [Rh(COD)-(S)-BINAP]BF4 ...............................................................................53 3.2.3 Activation of homogeneous catalyst precursors ........................................................55