Phosphate Substituted Dithiolene Complexes as Models for the Active Site of Molybdenum Dependent Oxidoreductases I n a u g u r a l d i s s e r t a t i o n zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Greifswald vorgelegt von Mohsen Ahmadi Greifswald, October 2019 . Dekan: Prof. Dr. Werner Weitschies 1. Gutachter : Prof. Dr. Carola Schulzke 2. Gutachter: Prof. Dr. Konstantin Karaghiosoff Tag der Promotion: 07.10.2019 . To my lovely wife Zahra and my little princess Sophia . Table of Contents Table of Contents Table of Contents ....................................................................................................................................... i Abbreviation and Symbols ....................................................................................................................... iii List of Compounds .................................................................................................................................... v Introduction .............................................................................................................................................. 1 1.1 Phosphorous and Molybdenum in Biology ......................................................................................... 3 1.2 Biosynthesis and Biological Screening of Moco .................................................................................. 7 1.3 Molybdopterin Models ....................................................................................................................... 9 1.3.1 Dithiolene Approach ...................................................................................................................... 10 1.3.2 The Pyrazine-Pyrane Approach ...................................................................................................... 14 1.3.3 The Pterin Approach ...................................................................................................................... 15 1.3.4 The Phosphate Approach ............................................................................................................... 17 1.4 Properties of Metal Dithiolene Complexes ....................................................................................... 20 1.5 Aim of Research ................................................................................................................................ 21 Results and Discussions........................................................................................................................... 25 2 Substituent Effects of MoIVO Bis(Dithiolene) Complexes .................................................................... 25 2.1 Background and Aims ....................................................................................................................... 25 2.2 Syntheses .......................................................................................................................................... 26 2.2.1 Ligand Synthesis ............................................................................................................................. 26 2.2.2 Complexation ................................................................................................................................. 28 2.3 Spectroscopic, Electronic, and Structural Studies ............................................................................. 29 2.3.1 Characterization of Ligands ............................................................................................................ 29 2.3.2 Characterization of Complexes ...................................................................................................... 35 2.4 OAT Catalysis ..................................................................................................................................... 59 2.5 Chapter summary .............................................................................................................................. 63 3 Unexpected Results and Obstacles ...................................................................................................... 65 3.1 Dianionic Mixed-Valence Nickel Dithiolene Cluster .......................................................................... 65 3.1.1 Background .................................................................................................................................... 65 3.1.2 Syntheses ....................................................................................................................................... 65 3.1.3 Spectroscopic, Electronic, and Structural Studies .......................................................................... 66 3.2 Synthesis of 4-(2-Oxo-1,3-dithiol-4-yl)-3a,4,5,6-tetrahydrobenzo[d][1,3]dithiol-2-one (16) ........... 78 4. Phosphonate Dithiolene Models......................................................................................................... 81 4.1 Background ....................................................................................................................................... 81 4.2 Approaches to the Bio-Inspired Models ........................................................................................... 81 4.3 Results and Discussion ...................................................................................................................... 82 4.3.1 Cycloaddition Approach ................................................................................................................. 82 4.3.2 Dithiocarbonate Approach ............................................................................................................. 84 4.4 Complexation .................................................................................................................................... 95 4.5 Chapter summary .............................................................................................................................. 96 5 Sophisticated mpt-Models Addressing the Phosphate Moiety ........................................................... 97 5.1 Background and Aims ....................................................................................................................... 97 i Table of Contents 5.2 Pterin-phosphonate approach .......................................................................................................... 97 5.3 Chapter summary ............................................................................................................................ 116 Conclusion ............................................................................................................................................. 117 6 Ongoing and Future Investigations .................................................................................................... 119 6.1 Thesis summary .............................................................................................................................. 119 6.2 Future Direction .............................................................................................................................. 120 Experimental ......................................................................................................................................... 123 7.1 General ............................................................................................................................................ 125 7.2 Physical Methods ............................................................................................................................ 125 7.2.1 Electrochemistry .......................................................................................................................... 126 7.2.2 Computational Chemistry ............................................................................................................ 126 7.2.3 Catalytic procedure ...................................................................................................................... 127 7.2.4 Determinations of pKa values ....................................................................................................... 127 7.2.5 X-ray crystallography ................................................................................................................... 127 7.3 Synthesis and Characterization ....................................................................................................... 128 Appendix ............................................................................................................................................... 153 References ............................................................................................................................................ 162 Eigenständigkeitserklärung ................................................................................................................... 175 Lebenslauf ............................................................................................................................................. 177 Acknowledgments ................................................................................................................................. 179 ii Abbreviation Abbreviation and Symbols Å Ångstrøm Abs. Absorbance ATP Adenosine Triphosphate APCI Atmospheric-Pressure Chemical Ionization AO Aldehyde Oxidase AcOH Acetic acid