STIMULI-RESPONSIVE AND BIODEGRADABLE POLYMERS By MEGAN RAE HILL A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2018 © 2018 Megan Rae Hill To solving science ACKNOWLEDGMENTS First, I would like to thank my mother for inspiring me to become a strong, hardworking, and independent person. Her support and encouragement have allowed me to chase my dreams in both education and travel. I am grateful for the love and support of my sister, whose kindness and compassion continues to inspire me every day. I thank the friends that I have met throughout my life that make each day enjoyable and who continue to inspire me to become a better person – Alexander Pemba, Morgan Brett, Katie Fisher, Matthew Jaoudi, Carolyn Averback, and Lindsey DeRatt. I am especially grateful for Noah Burrell, for his limitless support, for his patience and compromise, and for being the best partner in life’s adventures. I am thankful for my entire graduate experience, which would not have been possible without my advisor, Prof. Brent Sumerlin. His continued belief in my abilities over the last seven years not only inspired me to attend graduate school, but also has made graduate school a successful and rewarding experience. Additionally, I want to thank Brent for the occasional music recommendations over the years, which were usually pretty good. I am grateful to George and Josephine Butler for their establishment of the Butler Polymer Research Laboratory, which continually promotes a collaborative and supportive environment, and to the Department of Chemistry at the University of Florida for the opportunity to earn my Ph.D. and for financial support. I thank Prof. Ken Wagener for his commitment to us as students, and never failing to make us feel important and included in the Butler Polymer Research Laboratory. I thank the rest of my committee members as well, Prof. Stephen Miller, Prof. Daniel Talham, and Prof. Jennifer Andrew, for their instruction and time. 4 I would like to thank the members of the Sumerlin research group, for their constant support, encouragement, and collaboration. I am grateful for the open atmosphere that allowed me to discuss many of the obstacles I reached in both research and life. I would like to thank Dr. Bryan Tucker, Dr. William Brooks, Nick Carmean, Tomo Kubo, Charles Easterling, and Georg Schulz in particular, for their helpful discussions concerning research, and the development of new research projects. I would like to thank Dr. Bryan Tucker for his friendship from our very first day of graduate school. Our daily conversations truly made me aspire to become a better scientist and human being. I would like to thank all of those who were involved in my research projects, and in particular, the graduate and undergraduate students who worked with me during my doctoral research, Sofia Goodrich, Courtney Ligon, Elliot Mackrell, Carl Forsthoefel, and Andrew Turner. Lastly, I would like to thank Prof. Philip Costanzo for his mentorship during my undergraduate career at California Polytechnic State University. I would have never understood the splendor of polymers if he had not taken me into his research group and patiently mentored me for four years. Some of my best memories originate from the time I spent in the lab with my ‘polymer family’ that I first established in his group. 5 TABLE OF CONTENTS page ACKNOWLEDGMENTS .................................................................................................. 4 LIST OF FIGURES .......................................................................................................... 9 LIST OF SCHEMES ...................................................................................................... 11 LIST OF ABBREVIATIONS ........................................................................................... 12 ABSTRACT ................................................................................................................... 14 CHAPTER 1 STIMULI-RESPONSIVE AND BIODEGRADABLE POLYMERS ............................ 16 1.1 Overview ....................................................................................................... 16 1.2 Stimuli-Responsive Materials ........................................................................ 16 1.3 Biodegradable Polymers ............................................................................... 18 1.4 Responsive and Biodegradable Natural Polymers ........................................ 19 1.5 Responsive and Biodegradable Synthetic Polymers ........................................ 23 1.5.1 Step-Growth Polymers ............................................................................ 25 1.5.2 Chain-Growth Polymers .......................................................................... 28 1.6 Properties and Applications of Responsive and Degradable Polymers ............ 32 1.7 Conclusion and Future Outlook ........................................................................ 34 2 RESEARCH OBJECTIVE ....................................................................................... 36 3 BIODEGRADABLE AND pH-RESPONSIVE NANOPARTICLES DESIGNED FOR SITE-SPECIFIC DELIVERY IN AGRICULTURE ............................................ 39 3.1 Overview ........................................................................................................... 39 3.2 Results and Discussion ..................................................................................... 43 3.2.1 Synthesis of Amphiphilic PSI Copolymers and Nanoparticle Formation .. 43 3.2.2 Loading of Model Hydrophobic Molecule Nile Red .................................. 47 3.2.3 Response of the Nanoparticle to Alkaline pH and Release of Nile Red... 49 3.2.4 Plant Toxicity ........................................................................................... 51 3.3 Conclusion ........................................................................................................ 53 3.4 Materials and Methods ...................................................................................... 53 4 ALTERNATING RADICAL RING-OPENING COPOLYMERIZATION AFFORDS HOMOGENEOUS INCORPORATION OF DEGRADABLE UNITS ........................ 59 4.1 Overview ........................................................................................................... 59 4.2 Results and Discussion ..................................................................................... 62 4.3 Conclusion ........................................................................................................ 73 6 4.3 Materials and Methods ...................................................................................... 74 4.3.1 Materials .................................................................................................. 74 4.3.2 Analytical Techniques .............................................................................. 74 4.3.3 Experimental Procedures ........................................................................ 75 5 TUNABLE AND FUNCTIONAL POLYESTER COPOLYMERS SYNTHESIZED BY ALTERNATING RADICAL RING-OPENING COPOLYMERIZATION OF 5,6- BENZO-2-METHYLENE-1,3-DIOXEPANE AND N-SUBSTITUTED MALEIMIDES .......................................................................................................... 80 5.1 Overview ........................................................................................................... 80 5.2 Results and Discussion ..................................................................................... 82 5.3 Conclusion ........................................................................................................ 91 5.4 Materials and Methods ...................................................................................... 91 5.4.1. Materials ................................................................................................. 91 5.4.2 Analytical Techniques .............................................................................. 92 5.4.3 Experimental Procedures ........................................................................ 94 6 CONCLUSION ...................................................................................................... 100 APPENDIX LOADING OF MODEL HYDROPHOBIC MOLECULE NILE RED ............................... 102 MALDI-ToF OF DEGRADED P(MPDL-ALT-NETMI) ................................................... 103 REACTION OF BMDO WITH MALEIC ANHYDRIDE .................................................. 104 ANALYSIS OF BMDO AND N-SUBSTITUTED MALEIMIDE COPOLYMERS ............ 105 LIST OF REFERENCES ............................................................................................. 108 BIOGRAPHICAL SKETCH .......................................................................................... 121 7 LIST OF TABLES Table page 3-1 Nanoparticle diameter and loading capacity of Nile red ...................................... 49 4-1 Polymerizations of MPDL and NEtMI ................................................................. 67 5-1 Copolymerization of BMDO with N-substituted maleimides ................................ 88 5-2 Functionalization of poly(BMDO-alt-TCTMI) with model thiols and amines ........ 89 8 LIST OF FIGURES Figure page 1-1 Stimuli-responsive polymers ............................................................................... 17 1-2 Chemical structures of some natural biodegradable