Construction, analysis, and modeling of complex reaction networks with RING A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Srinivas Rangarajan IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctor of Philosophy Advised by Prodromos Daoutidis and Aditya Bhan August 2013 c Srinivas Rangarajan 2013 ALL RIGHTS RESERVED Acknowledgments I would like to thank my advisors Profs. Prodromos Daoutidis and Aditya Bhan. They gave me enough freedom to pursue my ideas, encouraged collaborations, offered inter- esting problems to work on, and above all were always available for advice to sort out my problems, technical and otherwise. I thank the members of the Daoutidis group, with whom I shared my office, and the Bhan group, with whom I had valuable interaction time-to-time. I would like to specifically thank my colleagues in the Daoutidis group, Ana Torres, Alex Marvin, Dimitrios Georgis, Seongmin Heo, Adam Kelloway, and former members Dr. Sujit Jogwar, Prof. Fernando Lima, and Prof. Milana Trifkovic, with whom I have had innumerable engaging technical discussions on common research problems. Beyond work, I have also found good friends in them. The camaraderie in the group has been wonderful and has made our office, the Popcorn Lounge, the ideal place to work; I will forever cherish the 2 PM coffee breaks. I also want to thank my batchmates and friends in the department, especially, Dr. Reetam Chakrabarty, with whom I had many valuable discussions starting from my first few weeks in Minneapolis. I thank all my other friends that I have made and all the roommates I have had here in the last five years { life in Minneapolis would never have been the cherishable if not for them. I want to specifically thank Julie Prince, our graduate program co-ordinator; I ar- rived late in the US, and without her help in sorting out all the initial administrative paper work, driving me to the SSN office, etc., my first few weeks would have been i ii unmanageable. Prof. Eric Van Wyk and Ted Kaminski at the Department of Computer Science and Engineering have been great collaborators that have patiently worked with me over the last three-and-a-half years. They both have provided a lot of insights on the computer science aspect of this research, and I would like to thank both of them for this, especially Ted, from whom I learnt a lot about efficient computer programming methods. Lastly, I'd like to thank my family, back in India, for their complete and uncondi- tional love and support over the course of my PhD, without which it would have been impossible to come to a new country and remain focused on my research. iii To My Family Abstract Complex reaction networks are found in a variety of engineered and natural chemi- cal systems ranging from petroleum processing to atmospheric chemistry and includ- ing biomass conversion, materials synthesis, metabolism, and biological degradation of chemicals. These systems comprise of several thousands of reactions and species inter-related through a highly interconnected network. This thesis presents methods, computational tools, and applications that demonstrate that: (a) any complex network can be constructed automatically from a small set of initial reactants and chemical transformation rules, and (b) a given network can be analyzed in terms of identifying topological information such as reaction pathways, determining thermodynamically fea- sible routes, evaluating the spectrum of plausible and synthetically feasible compounds, exploring dominant routes to form experimentally observed products, and formulating and solving a rigorous kinetic model. A new computational tool called Rule Input Network Generator, or RING, has been developed to construct and analyze complex reaction networks. Given initial re- actants of a reaction system (e.g. the components of the feed to a reactor) and reaction rules that describe the possible chemical transformations that can occur, RING first constructs an exhaustive network of reactions and species consistent with the inputs. Inputs into RING are in the form an English-like domain specific language with syntax involving common chemistry parlance. The language compiler further catches erroneous chemistry rules, such as incorrect charge balance in a reaction rule, and heuristically iv v optimizes user-specified instructions to improve the speed of execution. RING, fur- ther, accepts \post-processing" instructions that allow for: (i) lumping, or grouping together isomers to reduce the size of the reaction network, (ii) \querying" the network to extract information such as reaction pathways and mechanisms that describe how an initial reactant is transformed into a specific product, (iii) calculating thermochemical properties of species and reactions to evaluate thermochemical feasibility of reaction steps, and (iv) formulating and solving rigorous microkinetic models of complex reac- tion networks. RING, thus, provides a \rule-based" framework to assemble and explore a complex reaction network. RING implements several algorithms, methods, and techniques from computer sci- ence, cheminformatics, and graph theory. The language has been developed using SIL- VER, a meta-languge for specifying attribute grammars, and COPPER, a parser gen- erator. The language is extensible in that independent additions can be incorporated to the original language to perform additional analysis without syntactical and semantic conflicts with the existing grammar. Algorithms from chemical graph theory and chem- informatics are adopted to (i) represent molecules as strings externally and as graphs internally, (ii) store reaction rules as graph transfomration rules, (iii) identify fragments in molecules that can serve as reaction centers through pattern matching, (iv) determine molecular characteristics such as shape (linear, branched, cyclic, etc.) and aromaticity, and (v) identify isomeric lumps through a new molecular hashing technique. Graph traversal algorithms are further employed by the post-processing modules to identify pathways and mechanisms. This thesis presents several case studies of application of RING in elucidating com- plex networks of reactions. First, when chemistry alone is known about the system, RING can be used to identify plausible mechanisms for product formation consistent with experimental observations; it can further be used to postulate possible experiments to discriminate between the alternative mechanisms. This has been demonstrated with a case study of glycerol and acetone conversion on solid Brønsted acid catalysts. Sec- ond, if molecular properties can be evaluated quickly using semi-empirical methods for a large number of species and compounds, RING can be used to identify species in the network that have desired physical properties and thermochemically favorable synthesis routes to form them. A case study on identifying fatty alcohols, in a spectrum of more than 60,000 compounds, that can potentially be used to make nonionic surfactants with desirable properties and their synthesis routes from biomass-derived oxygenates vi presents an application of this method. It was found that lauryl alcohol, a fatty al- cohol currently used to make surfactants, can be synthesized from biomass-oxygenates using a combination of metal, basic, and acid catalysts. It was also found that some of the intermediate synthesis steps could potentially be coupled to drive the overall re- action forward, or could benefit from using biphasic systems for immediate separation of products from reactants. Third, if activation barriers of each step in the reaction can be reliably predicted using semi-empirical methods, RING can be used to iden- tify dominant reaction mechanisms for converting reactants to experimentally observed products. This was demonstrated by analyzing the energetically favorable mechanisms for glycerol conversion to syn gas or 1,2-propane diol on transition metal catalysts such as Platinum, Palladium, Rhodium, and Ruthenium. It was found that glycerol would decompose to syn gas on Platinum and Palladium, while a significant selectivity to the diol can be obtained on Rhodium and Ruthenium, thus offering insights for designing catalysts for complex biomass conversion systems. Finally, if kinetic parameters and thermochemistry can be estimated apriori, RING can be used to formulate and solve rigorous microkinetic models to get quantitative information such as yield and selectiv- ity. This feature is demonstrated through a model developed for methanol conversion to hydrocarbons (MTH) on Brønsted acid catalyst HZSM-5. RING is generic in terms of chemistries it can handle and flexible in terms of the type of analysis that can be performed. This thesis posits that it can be used in conjunction with experimental and computational chemistry data to elucidate systems with complex reaction networks, especially in hydrocarbon processing and biomass conversion. Contents Acknowledgmentsi Abstract iv Table of Contents vii List of Tables xii List of Figures xiv 1 Introduction1 1.1 Construction and analysis of complex networks: Methods and challenges3 1.2 Rule Input Network Generator: Features..................5 1.3 Applications of RING............................5 1.3.1 Topological analysis and mechanism hypothesis of complex systems6 1.3.2 Identification of synthetically feasible compounds and synthesis routes.................................6 1.3.3 Mechanism elucidation of complex glycerol conversion network on transition metals...........................7 1.3.4