SYNTHESIS AND IMPROVEMENT OF SELF-HEALING BORONATE ESTER HYDROGELS By CHRISTOPHER CHI-LONG DENG 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 2017 © 2017 Christopher Chi-long Deng To friends and family and loved ones departed ACKNOWLEDGMENTS Numerous people have supported me to this point. I would like to thank all of my previous teachers throughout my education for the foundation they gave to me and the valuable work that they do for all students. I thank Dr. Yi Zhang for allowing me to work in her lab and gain valuable experience. I would also like to thank Dr. Bill Dolbier for sharing his passion for organic chemistry and assisting me in entering graduate school. Of course, I am grateful towards Dr. Brent Sumerlin for accepting me in his group. His expectations and guidance have been valuable in my scientific growth. Also, I would like to thank my committee of Dr. Ken Wagener, Dr. Stephen Miller, Dr. Adam Veige, and Dr. Anthony Brennan. I appreciate the time taken from their busy schedules and their advice over the years. I would also like to acknowledge the University of Florida, the Department of Chemistry, and the Butler Polymer Laboratory for the opportunity to pursue my doctorate and providing a supportive environment for myself and all graduate students. I am grateful to the members of the Sumerlin group. I have the most interaction with them on a daily basis, and it has been a tremendous source of support both personally and professionally. I acknowledge Dr. Will Brooks, my first lab mate, for sharing in the agony of boronic acids, his general advice, and his friendship. I also thank Chris Kabb for being my second lab mate, providing great advice, and putting up with me in general. I also extend my gratitude towards Dr. Bryan Tucker and Megan Hill for being the “original” UF Sumerlin group members. You two were great friends, and together we occupied a unique position in the history of the Sumerlin lab. I thank Nick Carmean for being my on and off again workout partner and entertaining my automotive fantasies. Maybe the rally car dream will come true one day. Finally, I thank my family. I know that I don’t reach out as much as I should, but I appreciate that you are always there for me if I need it. 4 TABLE OF CONTENTS page ACKNOWLEDGMENTS ...............................................................................................................4 LIST OF TABLES ...........................................................................................................................8 LIST OF FIGURES .........................................................................................................................9 LIST OF SCHEMES......................................................................................................................13 LIST OF ABBREVIATIONS ........................................................................................................14 ABSTRACT ...................................................................................................................................16 CHAPTER 1 SYNTHESIS AND APPLICATIONS OF BORONIC ACID HYDROGELS.......................18 1.1 Introduction .......................................................................................................................18 1.2 Boronic Acid Hydrogels ...................................................................................................20 1.2.1 Early Examples of Boronic Acid Hydrogels ..............................................................20 1.2.2 A Brief Introduction to Rheology ..............................................................................22 1.2.3 Self-healing Boronic Acid Hydrogels ........................................................................26 1.2.4 Intramolecularly-Coordinated Boronic Acids and Hydrogels Derived Thereof ........33 2 RESEARCH OBJECTIVE .....................................................................................................37 3 BORONATE ESTER HYDROGELS UNDERGO SELF-HEALING AT NEUTRAL AND ACIDIC PH ...................................................................................................................40 3.1 Introduction .......................................................................................................................40 3.2 Results and Discussion .....................................................................................................42 3.2.1 Synthesis of 2APBA Copolymers and Hydrogel Formation .....................................42 3.2.2 Investigation of Hydrogel Self-healing ......................................................................45 3.2.3 Rheological Studies ....................................................................................................45 3.2.4 Examining the Effect of Catechol Oxidation on Self-healing ...................................47 3.3 Conclusions.......................................................................................................................49 3.4 Experimental .....................................................................................................................50 3.4.1 Materials .....................................................................................................................50 3.4.2 Instrumentation and Characterization ........................................................................51 3.4.3 Synthesis of 2-Acrylamidopheynlboronic Acid Pinacol Ester (2APBAE) ................52 3.4.4 Synthesis of Poly(2APBA-co-DMA) (P(2APBA-co-DMA)) ....................................52 3.4.5 Synthesis of Poly(PFPA-co-DMA) (P(PFPA-co-DMA)) ..........................................53 3.4.6 Synthesis of Poly(DOPAAm-co-DMA) (P(DOPAAm-co-DMA).............................53 3.4.7 Hydrogel Synthesis ....................................................................................................54 5 4 CHANGE IN INTRAMOLECULARLY-COORDINATED BORONIC ACID MONOMER STRUCTURE RESULTS IN IMPROVED SELF-HEALING HYDROGEL PROPERTIES ..................................................................................................55 4.1 Introduction .......................................................................................................................55 4.2 Results and Discussion .....................................................................................................58 4.2.1 Synthesis of APAPBA Copolymers ...........................................................................58 4.2.2 Reactivity Ratio Studies of APAPBAE and 2APBAE ..............................................59 4.2.3 Hydrogel Formation, Transparency Comparison, and Self-healing Studies ..............61 4.2.4 Rheological Studies ....................................................................................................62 4.2.5 Effect of Buffer Concentration on Rheology .............................................................67 4.3 Conclusions.......................................................................................................................68 4.4 Experimental .....................................................................................................................68 4.4.1 Materials .....................................................................................................................68 4.4.2 Instrumentation and Characterization ........................................................................69 4.4.3 Synthesis of 3-Acrylamidopropanoic Acid ................................................................69 4.4.4 Synthesis of (2-(3-Acrylamidopropanamido)phenyl)boronic Acid Pinacol Ester (APAPBAE) ........................................................................................................................70 4.4.5 Synthesis of Poly(APAPBA-co-DMA) (P(APAPBA-co-DMA)) .............................71 4.4.6 Hydrogel Synthesis ....................................................................................................71 4.4.7 Reactivity Ratios ........................................................................................................71 5 TEMPERATURE INDUCED CONTROL OF SELF-HEALING AND STRESS RELAXATION IN DYNAMIC-COVALENT HYDROGELS .............................................73 5.1 Introduction .......................................................................................................................73 5.2 Results and Discussion .....................................................................................................75 5.2.1 Synthesis of APAPBA/NIPAM Copolymers and Cloud Point Determination ..........75 5.2.2 Examining the Effect of Temperature on Hydrogel Creep and Self-healing .............76 5.2.3 Temperature-Dependent Rheological Studies............................................................78 5.3 Conclusions.......................................................................................................................84 5.4 Experimental .....................................................................................................................86 5.4.1 Materials .....................................................................................................................86 5.4.2 Instrumentation and Characterization ........................................................................86 5.4.3 Synthesis of 3-Acrylamidopropanoic