New Solution to an Old Problem: Exploring Properties of Chemical Reactions in Condensed Phases Using Molecular Simulation Kelly L. Fleming A dissertation Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2015 Reading Committee: Jim Pfaendtner, Ph.D., Chair Xiaosong Li, Ph.D. Qiuming Yu, Ph.D. Scott Dunham, Ph.D., GSR Program Authorized to Offer Degree: Chemical Engineering ©Copyright 2015 Kelly L. Fleming Portions of this document have been published in academic journals with reprint permissions from the journal. Copyright attributions are provided at the beginning of each chapter for those that have been published prior to the submission of this document. i University of Washington Abstract New Solution to an Old Problem: Exploring Properties of Chemical Reactions in Condensed Phases Using Molecular Simulation Kelly L. Fleming Chair of the Supervisory Committee: Professor Jim Pfaendtner Chemical Engineering The study of chemical reactions is a foundation of chemical engineering, yet there are limited ways to examine how their properties are influenced. Our research has explored the use of molecular simulation to characterize reaction properties in varying environments. First, we use the most common method, Quantum Mechanics (QM) with a Density Functional Theory (DFT) model to study the hydrolysis of a glyosidic bond, which is important for the breakdown of biomass. Previously unknown detailed mechanistic steps were found for the hydrolysis reaction. The reaction was subsequently simulated with a continuum model in several different acid solvents, and the reaction energetics were shown to be directly related to the inverse of the dielectric constant. However, the mechanistic details were unchanged. Based on the trend observed between acid solvents, we set out to learn more about the way the solvents affect reaction properties. In order to accurately determine how solvent molecules affect the reaction, they must be modeled explicitly, as opposed to a continuum model. In order to facilitate fast computation in a reasonable timeframe, we overcame computational limitations stemming from the explicit solvent molecules by pairing a ii multiscale modeling approach known as metadynamics with the Car Parrinello molecular dynamics method. We observed a stabilizing effect from the solvent. However, after several failed attempts to quantify the barrier heights, we discovered that this approach does not lead to reproducible or accurate estimates for reaction barriers, despite being the consensus approach in literature. Instead of purely using metadynamics, we demonstrated for the first time that a method called “MetaRates” can be used to make estimates of a chemical reaction rate. This was an exciting addition to a method that previously had not been used to study systems with ab initio potentials. In a detailed investigation, we were able to demonstrate that this method is successfully used to predict the energy barrier heights that match with quantum mechanics. Based on our work, we believe that MetaRates can be used to model more complex reactions, such as those taking place in enzymes, on surfaces, and in complex solvents like those we are interested in for continuing biomass reaction research. iii I Acknowledgements and Dedication My progress through the PhD program has greatly hinged on the help of others in the Pfaendtner Research Group. I could not have completed the program without support from every member of our group, and most importantly Professor Pfaendtner, to develop my intuition and knowledge about computers, physical and organic chemistry, and the scientific research process. Particularly, the help and support of Vance Jaeger, Pat Burney, Mike Deighan, Kayla Sprenger, Michael Tung, and Sean Fischer were crucial in advancing me through the program. In addition to developing me as a researcher, Professor Pfaendtner has encouraged and aided in my career goals, and helped me develop into the professional I strived to be upon graduation. Additionally I would like to dedicate this dissertation the many friends and family members, near and far, who have supported me during my graduate tenure through helping me develop as a professional and encouraging me to further my career in science. My parents have been essential in setting me up for success since I was born, and I will never be able to repay them for that except for in my efforts to continue to strive for my goals. I especially would like to thank Alice Popejoy and Melanie Roberts for encouraging my involvement in the Graduate and Professional Student Senate and the Science Policy Committee at the University of Washington, which have been pivotal in my professional development. Not only have they given me professional advice and supported me through recommendations, but they have been there for me with the inspiring words of friends through tough times. iv Table of Contents I Acknowledgements and Dedication ......................................................................................... iv Table of Figures ........................................................................................................................... viii 1 Preface ....................................................................................................................................... 1 2 Introduction ............................................................................................................................... 3 2.1 Background ............................................................................................................. 3 2.2 Motivation ............................................................................................................... 6 2.2.1 Increasing the efficiency of the degradation of cellulosic materials to produce biofuels .................................................................................................................... 6 3 Characterizing the Catalyzed Hydrolysis of β-1, 4 Glycosidic Bonds Using Density Functional Theory ................................................................................................................... 11 3.1 Abstract ................................................................................................................. 11 3.2 Introduction ........................................................................................................... 12 3.3 Methods................................................................................................................. 14 3.3.1 Systems and Structures Modeled .................................................................. 14 3.3.2 DFT calculations and solvation model ......................................................... 16 3.3.3 Locating energy minima and transition states .............................................. 17 3.4 Results and Discussion ......................................................................................... 18 3.4.1 A fully atomistic view of the double displacement reaction mechanism ..... 18 3.4.2 Comparison to the uncatalyzed reaction mechanism .................................... 23 v 3.4.3 Effects of solvation ....................................................................................... 25 3.4.4 Effects of varying the solvent type ............................................................... 27 3.4.5 Effects of ring substituent groups ................................................................. 30 3.5 Conclusions ........................................................................................................... 32 4 Ab initio molecular dynamics with metadynamics to study reactions involved in biomass conversion in solvents ............................................................................................................. 35 4.1 Abstract ................................................................................................................. 35 4.2 Introduction ........................................................................................................... 36 4.2.1 Esterification reactions in ionic liquids ......................................................... 39 4.2.2 Hydrolysis reactions in ionic liquids ............................................................. 41 4.3 Methods................................................................................................................. 44 4.3.1 Ab initio molecular dynamics with metadynamics to study reactions in solvents ................................................................................................................. 44 4.3.2 Modeling esterification reactions in gas, water, and ionic liquid mixtures .. 46 4.3.3 Modeling hydrolysis reactions in gas, water, and ionic liquids .................... 48 4.4 Results and Discussion ......................................................................................... 50 4.4.1 Solvation effects on the physical and chemical properties of esterification reactions ................................................................................................................ 50 4.4.2 Solvation effects on physical properties of hydrolysis reactions to break down biomass........................................................................................................ 57 4.5 Conclusions ........................................................................................................... 59 vi 5 A New Approach for Investigating