THEORETICAL STUDIES OF STRUCTURES AND MECHANISMS IN ORGANOMETALLIC AND BIOINORGANIC CHEMISTRY: HECK REACTION WITH PALLADIUM PHOSPHINES, ACTIVE SITES OF SUPEROXIDE REDUCTASE AND CYTOCHROME P450 MONOOXYGENASE, AND TETRAIRON HEXATHIOLATE HYDROGENASE MODEL A Dissertation by PANIDA SURAWATANAWONG Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2009 Major Subject: Chemistry THEORETICAL STUDIES OF STRUCTURES AND MECHANISMS IN ORGANOMETALLIC AND BIOINORGANIC CHEMISTRY: HECK REACTION WITH PALLADIUM PHOSPHINES, ACTIVE SITES OF SUPEROXIDE REDUCTASE AND CYTOCHROME P450 MONOOXYGENASE, AND TETRAIRON HEXATHIOLATE HYDROGENASE MODEL A Dissertation by PANIDA SURAWATANAWONG Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved by: Chair of Committee, Michael B. Hall Committee Members, Robert R. Lucchese Yi-Qin Gao Perla Balbuena Head of Department, David H. Russell May 2009 Major Subject: Chemistry iii ABSTRACT Theoretical Studies of Structures and Mechanisms in Organometallic and Bioinorganic Chemistry: Heck Reaction with Palladium Phosphines, Active Sites of Superoxide Reductase and Cytochrome P450 Monooxygenase, and Tetrairon Hexathiolate Hydrogenase Model. (May 2009) Panida Surawatanawong, B.S., Mahidol University Chair of Advisory Committee: Dr. Michael B. Hall The electronic structures and reaction mechanisms of transition-metal complexes can be calculated accurately by density functional theory (DFT) in cooperation with the continuum solvation model. The palladium catalyzed Heck reaction, iron-model complexes for cytochrome P450 and superoxide reductase (SOR), and tetrairon hexathiolate hydrogenase model were investigated. The DFT calculations on the catalytic Heck reaction (between phenyl-bromide and ethylene to form the styrene product), catalyzed by palladium diphosphine indicate a four-step mechanism: oxidative addition of C 6H5Br, migratory insertion of C 6H5 to C2H4, β-hydride transfer/olefin elimination of styrene product, and catalyst regeneration by removal of HBr. For the oxidative addition, the rate-determining step, the reaction through monophosphinopalladium complex is more favorable than that through either the diphosphinopalladium or ethylene-bound monophosphinopalladium. In further t study, for a steric phosphine, P Bu 3, the oxidative-addition barrier is lower on iv monopalladium monophosphine than dipalladium diphosphine whereas for a small phosphine, PMe 3, the oxidative addition proceeds more easily via dipalladium diphosphine. Of the phosphine-free palladium complexes examined: free-Pd, PdBr -, and 2 Pd( η -C2H4), the olefin-coordinated intermediate has the lowest barrier for the oxidative- addition. P450 and SOR have the same first-coordination-sphere, Fe[N 4S], at their active sites but proceed through different reaction paths. The different ground spin states of the III intermediate Fe (OOH)(SCH 3)(L) model {L = porphyrin for P450 and four imidazoles for SOR} produce geometric and electronic structures that assist i) the protonation on distal oxygen for P450, which leads to O-O bond cleavage and formation of IV (Fe =O)(SCH 3)(L) + H2O, and ii) the protonation on proximal oxygen for SOR, which III leads to (Fe -HOOH)(SCH 3)(L) formation before the Fe-O bond cleavage and H 2O2 production. The hydrogen bonding from explicit waters also stabilizes Fe III -HOOH over IV Fe =O + H 2O products in SOR. The electrochemical hydrogen production by Fe 4[MeC(CH 2S) 3]2(CO) 8 (1) with 2,6-dimethylpyridinium (LutH +) were studied by the DFT calculations of proton-transfer free energies relative to LutH + and reduction potentials (vs. Fc/Fc +) of possible intermediates. In hydrogen production by 1, the second, more highly reductive, applied potential (-1.58 V) has the advantage over the first applied potential (-1.22 V) in that the more highly reduced intermediates can more easily add protons to produce H 2. v DEDICATION To my parents, Jirasak and Chomchuen. vi ACKNOWLEDGEMENTS I would like to thank Dr. Michael B. Hall, my advisor, for the opportunities to learn and to do research under his guidance and support throughout my graduate study. I also would like to thank all my committee members, Dr. Robert Lucchese, Dr. Yi-Qin Gao, Dr. Perla Balbuena, and Dr. Bart Childs for their advice. Thanks also to all of the members in Dr. Hall’s research group: Yubo Fan, Ben Vastine, Hong Wu, Xinzheng Yang, Chad Beddie, Charles Edwin Webster, Jesse Tye, Christine Thomas, and Lisa Perez for their advice and discussion. Special thanks go to Yubo Fan for all his help from the very beginning of my graduate research, Ben Vastine for his help in my research writing and presentation during the time of my study, and Lisa Perez for her help in the use of computer software. Thanks also go to Aleksander Wojcik for his support and discussion. I also would like to acknowledge DPST scholarship from Thailand, which provides part of the funding for my study through undergraduate and graduate schools. vii TABLE OF CONTENTS Page ABSTRACT .............................................................................................................. iii DEDICATION .......................................................................................................... v ACKNOWLEDGEMENTS ...................................................................................... vi TABLE OF CONTENTS .......................................................................................... vii LIST OF FIGURES ................................................................................................... x LIST OF TABLES .................................................................................................... xiii CHAPTER I INTRODUCTION ................................................................................ 1 1.1 Palladium catalyzed Heck reaction .......................................... 3 1.2 Iron enzyme models ................................................................. 5 II THEORETICAL METHODS .............................................................. 8 2.1 Hartree product wave function ................................................. 10 2.2 Antisymmetric wave function .................................................. 10 2.3 Hartree-Fock approximation .................................................... 13 2.4 Basis set approximation ........................................................... 14 2.5 Mulliken population analysis ................................................... 16 2.6 Basis functions ......................................................................... 17 2.7 Effective core potential ............................................................ 19 2.8 The electron correlation ........................................................... 22 2.9 Density functional theory ......................................................... 23 2.10 Geometry optimization ........................................................... 27 2.11 The partition function ............................................................. 30 2.12 Transition state theory ............................................................ 33 2.13 Continuum solvation model ................................................... 35 viii CHAPTER Page III DENSITY FUNCTIONAL STUDY OF THE COMPLETE PATHWAY FOR THE HECK REACTION WITH PALLADIUM DIPHOSPHINES ......................................................... 43 3.1 Introduction ............................................................................. 43 3.2 Computational details ............................................................... 47 3.3 Results and discussion .............................................................. 48 3.3.1 The oxidative addition .................................................... 49 3.3.2 The migratory insertion, β-hydride transfer/olefin elimination, and catalyst recovery .................................. 57 3.4 Conclusions .............................................................................. 66 IV THEORETICAL STUDY OF ALTERNATIVE PATHWAYS FOR THE HECK REACTION THROUGH DIPALLADIUM AND “LIGAND-FREE” PALLADIUM INTERMEDIATES ............. 69 4.1 Introduction ............................................................................. 69 4.2 Computational details ............................................................... 71 4.3 Results and discussion .............................................................. 72 4.3.1 Pre-catalytic reaction ...................................................... 73 4.3.2 The oxidative addition to dipalladium, Pd 2(PR 3)2 ........... 78 4.3.3 The oxidative addition to substrate-bound palladium ..... 80 4.3.4 The migratory insertion, β-hydride transfer/olefin elimination, and catalyst recovery of dipalladium .......... 84 4.3.5 The migratory insertion, β-hydride transfer/olefin elimination, and catalyst recovery of substrate-bound palladium ......................................................................... 89 4.4 Conclusions .............................................................................. 97 V DENSITY FUNCTIONAL STUDY OF THE FACTORS AFFECTING THE PRODUCTS FORMED BY CYTOCHROME P450 AND SUPEROXIDE REDUCTASE: INTERMEDIATE SPIN STATES AND HYDROGEN BONDS FROM WATER SOLVENT MOLECULES .................................................................. 99 5.1 Introduction ............................................................................