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© 2019 Jialin Mao ALL RIGHTS RESERVED © 2019 Jialin Mao ALL RIGHTS RESERVED CHARACTERIZATION OF POLYMER ARCHITECTURES AND SEQUENCES BY MULTI-STAGE MASS SPECTROMETRY A Dissertation Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Jialin Mao May, 2019 CHARACTERIZATION OF POLYMER ARCHITECTURES AND SEQUENCES BY MULTI-STAGE MASS SPECTROMETRY Jialin Mao Dissertation Approved: Accepted: _________________________________ _________________________________ Advisor Department Chair Dr. Chrys Wesdemiotis Dr. Christopher J. Ziegler _________________________________ ________________________________ Committee Member Dean of the College Dr. Wiley J. Youngs Dr. Linda Subich _________________________________ ________________________________ Committee Member Executive Dean of the Graduate School Dr. Adam W. Smith Dr. Chand Midha _________________________________ _________________________________ Committee Member Date Dr. Aliaksei Boika _________________________________ Committee Member Dr. Toshikazu Miyoshi ii ABSTRACT This dissertation focuses on the characterization of polymer architectures and sequences by tandem and multi-stage mass spectrometry (MS2 and MSn) as well as ion mobility mass spectrometry (IM-MS). The experiments described in this dissertation utilized matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) as ionization techniques and collisionally activated dissociation (CAD), electron transfer dissociation (ETD), and laser-induced fragmentation (LIFT) as ion activation and dissociation techniques. Polymers studied include an 8-shaped polystyrene, star-branched polyethers, monodisperse sequence-defined POSS-functionalized polyesters, and poly(t- butyl methacrylate). A well-defined 8‑shaped polystyrene was characterized by MALDI-MS, MALDI- MS2, and IM-MS. 8-shaped polymers could have inter and intra isomers which cannot be distinguished by single stage mass spectrometry. MALDI-MS2 of 8‑shaped polystyrene showed specific fragment species that can only be produced by the inter isomer, thus confirming the existence of the inter isomer. The degree of branching and the length of individual branches of a set of mikto- and homo-arm star polyethers were studied by MALDI-MS2 and ESI-MS2. The number of fragment distributions combined with the mass to charge ratios of the fragment ions iii gave conclusive evidence for the number of branches in the star polyethers and the corresponding branch lengths. A set of monodisperse, sequence-defined, and POSS-functionalized polyester copolymers were analyzed by MALDI-MS2. Isomeric oligomers with different sequences were readily distinguished by their different fragmentation patterns. Oligomers up to hexamers were successfully sequenced based on the specific backbone fragment species observed. The backbone connectivity of poly(t-butyl methacrylate) (PtBMA) was investigated by tandem and multistage mass spectrometry. The results showed that ETD- MS2 and ETD-CAD-MS3 enable backbone C-C bond cleavages and, thus, provides the chain connectivity information needed to characterize end groups and acrylate (co)polymer sequences. The studies presented in this dissertation emphasize the capability of mass spectrometry as a powerful technique for the characterization of architectures and sequences of a variety of synthetic polymers. iv DEDICATION To my family, without your endless love and support, I couldn’t have completed this. v ACKNOWLEDGMENTS I would like to express my deepest gratitude to my advisor Dr. Chrys Wesdemiotis for his permanent guidance, support, and valuable influence in my doctoral research. I extend my gratitude to my committee members Dr. Wiley J. Youngs, Dr. Adam W. Smith, Dr. Aliaksei Boika and Dr. Toshikazu Miyoshi for their guidance and valuable insight to elevate the quality of my research. I would like to thank all my former and current group members: Dr. Lydia Cool, Dr. Ahlam Alawiat, Dr. Nick Alexander, Dr. Sahar Sallam, Dr. Selim Gerislioglu, Michelle Kushnir, Ivan Dolog, Dr. Kevin Endres, Savannah Snyder, Jason O’Neil, Kayla Williams-Pavlantos, Chen Du and Benqian Wei for their support, friendship and helpful discussions. I would like to thank my collaborators: Dr. Qiming He in Dr. Mark D. Foster’s group, Dr. Wei Zhang, Zhiwei Lin, Xueyan Feng, Bo Ni in Dr. Stephen Z.D. Cheng’s group, Yusheng Chen in Dr. Matthew Becker’s group, and Dr. Scott M. Grayson, for their input, suggestions and great collaborations. I would like to thank you husband, Dr. Wenbin Yin, and my Parents, Guozhang Mao and Jinping Zhang, for their support. vi TABLE OF CONTENTS LIST OF FIGURES ........................................................................................................... xi LIST OF SCHEMES....................................................................................................... xvii LIST OF TABLES ............................................................................................................ xx CHAPTER I. INTRODUCTION....................................................................................................... 1 II. MASS SPECTROMETRY BACKGROUND ............................................................... 5 2.1 Introduction ............................................................................................................... 5 2.2 Inlet System ............................................................................................................... 6 2.3 Ion Source ................................................................................................................. 6 2.3.1 Electrospray Ionization (ESI) ............................................................................. 7 2.3.2 Matrix-Assisted Laser Desorption Ionization (MALDI) .................................. 11 2.4 Mass Analyzers ....................................................................................................... 13 2.4.1 Quadrupole Mass Analyzer .............................................................................. 14 2.4.2 Time-of-Flight (ToF) Mass Analyzer ............................................................... 16 2.4.3 Quadrupole/Time-of-Flight (Q/ToF) Mass Analyzer ....................................... 19 2.4.4 Quadrupole Ion Trap (QIT) Mass Analyzer ..................................................... 20 vii 2.5 Ion Detector ............................................................................................................. 23 2.6 Ion Mobility-Mass Spectrometry (IM-MS) ............................................................. 24 2.7 Tandem Mass Spectrometry (MS/MS) ................................................................... 27 III. MATERIALS AND INSTRUMENTATION ............................................................... 30 3.1 Materials .................................................................................................................. 30 3.2 Instrumentation ........................................................................................................ 31 3.2.1 MALDI ToF/ToF Mass Spectrometer .............................................................. 31 3.2.2 Synapt HDMS Quadrupole/Time-of-Flight (Q/ToF) Mass Spectrometer ....... 32 3.2.3 Bruker HCT Ultra Quadrupole Ion Trap Mass Spectrometer .......................... 34 IV. MALDI TANDEM MASS SPECTROMETRY (MALDI-MS2) AND .............................................................................................................. 36 4.1 Background ............................................................................................................. 36 4.2 Materials and methods ............................................................................................ 38 4.2.1 8-Shaped Polystyrene ....................................................................................... 38 4.2.2 Mass Spectrometry ........................................................................................... 38 4.3 Results and Discussion ............................................................................................ 41 4.3.1 Characterization of 8-Shaped Polystyrene by MALDI-ToF/ToF-MS ............. 41 4.3.2 Advanced Isomer Characterization Using Mass Spectrometry ........................ 43 4.4 Conclusion ............................................................................................................... 55 viii V. ELUCIDATING BRANCHING TOPOLOGY AND BRANCH ........................................................................................................... 56 5.1 Background ............................................................................................................. 56 5.2 Materials and methods ............................................................................................ 58 5.2.1 Mass Spectrometry ........................................................................................... 58 5.2.2 Star-Branched Polyethers ................................................................................. 60 5.3 Results and Discussion ............................................................................................ 61 5.3.1 Two-Arm Mikto-Star (2-kDa and 750-Da PEG Arms) .................................... 65 5.3.2 Two-Arm Homo-Star (2-kDa PEG Arms) ....................................................... 74 5.3.3 Three-Arm Homo-Star (2-kDa PEG Arms) ..................................................... 75 5.4 Conclusions ............................................................................................................
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