Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 5-2014 Quantum Mechanical Study of Weak Molecular Interactions Upendra Adhikari Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Biochemistry Commons Recommended Citation Adhikari, Upendra, "Quantum Mechanical Study of Weak Molecular Interactions" (2014). All Graduate Theses and Dissertations. 2184. https://digitalcommons.usu.edu/etd/2184 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. QUANTUM MECHANICAL STUDY OF WEAK MOLECULAR INTERACTIONS by Upendra Adhikari A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Chemistry Approved: __________________ __________________ Steve Scheiner Tapas Kar Major Professor Co-Advisor __________________ __________________ David Farrelly Alexander I. Boldyrev Committee Member Committee Member __________________ __________________ Bradley S. Davidson T. C. Shen Committee Member Committee Member ________________ Mark R. McLellan Vice President for Research and Dean of the School of Graduate Studies UTAH STATE UNIVERSITY Logan, Utah 2014 ii Copyright © Upendra Adhikari 2014 All Rights Reserved iii ABSTRACT Quantum Mechanical Study of Weak Molecular Interactions by Upendra Adhikari, Doctor of Philosophy Utah State University, 2014 Major Professor: Dr. Steve Scheiner Co-Advisor: Dr. Tapas Kar Department: Chemistry and Biochemistry Noncovalent interactions have a long history and have received huge attention since their discovery almost a century ago. The prevalence of noncovalent interactions can be seen in the formation of simple dimers to structural and functional modification of large biomolecules. Even though plenty of experimental and theoretical studies are performed to understand various noncovalent interactions, the nature and variety of those interactions are still subject of study. And still they are receiving tremendous attention due to their significant role in the stability and conformation of biomolecules, catalysis of organic and inorganic reactions, crystal packing and material design. This dissertation explores various new sorts of noncovalent interactions, compares them with existing ones, and extensively studies the relevance of noncovalent interactions to various biological systems of interest by applying quantum mechanical tools. A new sort of noncovalent interaction has been identified where two electronegative atoms interact directly with each other with no intervening hydrogen or halogen atoms. These iv interactions are found to be surprisingly strong, even stronger than regular OH···O and NH···O hydrogen bonds in some cases, and are stabilized by the charge transfer from electron donor to electron acceptor. The major portion of this dissertation deals with the rigorous investigation of new sorts of interactions like P···N, S···N, Cl···N and several other charge transfer types of interactions with side by side comparison with hydrogen and halogen bonds. Similarly, a new carbonyl-carbonyl stacking geometry in peptide- peptide interactions is explored. These stacking geometries are energetically close to stronger NH···O hydrogen bonds, and get some assistance from CH···O hydrogen bonds. Carbon is considered one of the potent H-bond donors, albeit weaker, due to its ubiquitous presence in biomolecules. So, another portion of this dissertation is focused on the study of neutral and charged CH hydrogen bonds simulating various interpeptide interactions and enzyme catalysis. And the last part of this dissertation deals with the putative H-bonds that might be present in tip functionalized carbon nanotubes. (414 pages) v PUBLIC ABSTRACT Quantum Mechanical Study of Weak Molecular Interactions Upendra Adhikari, Doctor of Philosophy Molecular interactions play key role in the existence of biomolecules like proteins and nucleic acids, and various materials. Molecular interactions are weak forces that hold different molecules or different fragments of the same molecule together, and are often referred to as noncovalent interactions. Due to the complexity in biomolecules, these interactions are still poorly understood. This dissertation presents results from quantum mechanical simulations of various types of noncovalent interactions, which are extremely important for the structure and functions of biomolecules and materials. A new sort of noncovalent interaction is identified. This new sort of interaction originates from a direct interaction between two electronegative atoms. This interaction is represented as BA···D, where A and D are electronegative atoms, and B is some substituent. In most cases, this new sort of interaction is found to be more stable than regular hydrogen bonds. These new interactions are found to have some potential to allow the development of materials with unusual physical properties. This dissertation also explores the role of supposedly weaker CH hydrogen bonds on the configuration of peptide-peptide interactions, secondary structure of proteins, and mechanism of methyl transfer reaction in enzymes. Similarly, putative hydrogen bonding at the tips of functionalized carbon nanotubes is studied, which reveals the absence of OH and COOH groups together at the tips of carbon nanotubes. vi ACKNOWLEDGMENTS I would like to express my sincere gratitude to my advisor, Professor Steve Scheiner, for his continuous support, proper guidance and exceptional mentoring. I am indebted to him for his encouragement, inspiration and helping me grow as a better student, researcher and as a better person. I am also grateful to my co-advisor, Dr. Tapas Kar, for his invaluable support, cooperation and motivation. I would like to thank my supervisory committee members, Dr. Bradley S. Davidson, Dr. David Farrelly, Dr. Alexander I. Boldyrev and Dr. T. C. Shen, for their priceless time and valuable suggestions. I would like to thank all my colleagues, friends, and Nepali community in Logan for their wonderful companionship and support during my graduate study. Especially, I am grateful to Shuangkou Chen, Jared Moss, Binod Nepal, Jaya Shrestha, Vincent Nziko, Prakash Joshi, Sanjib Shrestha, Ram Neupane, and Jay Bhattarai. Next, I want to thank the Department of Chemistry and Biochemistry, Utah State University for providing me the opportunity to pursue my scientific career. Computer, storage and other resources from the Division of Research Computing in the Office of Research and Graduate Studies at Utah State University are gratefully acknowledged. Similarly, I am grateful to the Office of Research and Graduate Studies, Utah State University for granting me the Dissertation Fellowship which eased my dissertation writing. Most importantly, I would like to thank my parents for their continuous support, love and care throughout my life, without whom I would never get this achievement. vii Similarly, my thanks go to my siblings, Ishowar Adhikari, Rammaya Thapa and Krishna Kumari Khatri, and all of my relatives for their love and support. Especially, I would like to thank my wife, Sarita. Her support, love, patience and encouragement were crucial for this achievement. I am grateful to my son, Aarush, for giving countless happiness and endless joy in my life. Upendra Adhikari viii CONTENTS Page ABSTRACT ....................................................................................................................... iii PUBLIC ABSTRACT .........................................................................................................v ACKNOWLEDGMENTS ................................................................................................. vi LIST OF TABLES ........................................................................................................... xiii LIST OF FIGURES ......................................................................................................... xvi LIST OF ABBREVIATIONS ......................................................................................... xxii CHAPTER 1. INTRODUCTION ...................................................................................................1 References ..................................................................................................12 2. THE S∙∙∙N NONCOVALENT INTERACTION: COMPARISON WITH HYDROGEN AND HALOGEN BONDS.............................................................19 Abstract ..................................................................................................... 19 2-1. Introduction ........................................................................................19 2-2. Computational Methods .....................................................................21 2-3. Results ................................................................................................21 2-4. Conclusions ....................................................................................... 25 References ..................................................................................................27 3. ABILITIES OF DIFFERENT ELECTRON DONORS (D) TO ENGAGE IN A P∙∙∙D NONCOVALENT INTERACTION ........................................................34 Abstract ......................................................................................................34