Dynamic Covalent Assembly of Abiotic, Information-bearing Oligomers by Tao Wei A dissertation

247 Pages·2017·15.42 MB·English

Dynamic Covalent Assembly of Abiotic, Information-bearing Oligomers

by

Tao Wei

A dissertation submitted in partial fulfillment
of the requirements for the degree of
Doctor of Philosophy
(Chemical Engineering)
in The University of Michigan
2017

Doctoral Committee:

Assistant Professor Timothy F. Scott, Chair
Professor Mark A. Barteau
Professor Joerg Lahann
Professor Anne McNeil
Tao Wei

[email protected]

ORCID ID: 0000-0001-8923-293X

© Tao Wei 2017
DEDICATION

This dissertation is dedicated to
Liang
Mom and Dad
Suying and Xuexian
For their love and endless support

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ACKNOWLEDGEMENTS

I would like to thank my PhD advisor Prof. Timothy F. Scott for his support,
guidance, patience, encouragement, and wisdom throughout my doctoral studies at the
University of Michigan. I would also like to express my gratitude to my dissertation
committee members, Professor Mark Barteau, Professor Joerg Lahann and Professor
Anne McNeil for their constructive discussions and advice.
I am fortunate to have met many talented and fun individuals throughout my PhD.
Some of these amazing people include Jin Ge, Ray Seo, Wenjun Huang, Molly
Kozminsky, Jeff Lowe, Eric and Jai Holt, Lynn Secondo, Xiaozhou Sheng and Ziyong
Lin; I am grateful for our fun times. I cannot thank these individuals enough for their
support and friendship.
I must emphasize how lucky I am to have extremely supportive and encouraging lab
mates including Dr. Scott Zavada, Dr. Joseph Furgal, Dowon Ahn, Megan Dunn, Harry
van der Laan, Max Ma, Samuel Leguizamon, Abdulla Alqubati, Austin Bingham, Dr. Jae
Hwan Jung, Dr. Jungting Li, Sameer Sathe, and Dan Li. I want to thank them for building
the family atmosphere of Polymer Dojo and I really appreciate their friendship.
Especially, I want to thank Scott, Dowon, and Megan for their invaluable help in building
the lab in early years. I want to mention Scott, who’s always been a great friend and a
mentor, for his kind advice on research and life. I want to thank Megan and Sam for their
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support and I really enjoyed our discussions over Pokémon and doing raid battles
together. I am also fortunate enough to have worked with Joe and Jae Hwan on various
projects, from whom I learned a lot. In addition, I want to acknowledge Harry for his
effort on maintaining a safe lab environment.
I am also very grateful to Professor Greg Thurber at U-M and Thurber lab members
for their help on instrumentation such as high performance liquid chromatography
(HPLC). Especially, I want to thank Liang Zhang and Submit Bhatnagar for their great
effort on the daily maintenance of HPLC and their help on HPLC trouble shooting.
Special thanks are in order to James Windak of the Chemistry Department Mass Spec
Services Lab for his help with determining molecule compositions. Gratitude is also
given to the U-M Chemical Engineering faculty and staff, especially Susan Hamlin, Kelly
Raickovich, Barbara Perry and Shelley Fellers for their assistance.
I would also like to acknowledge the funding that supported my graduate studies.
This includes the U.S. Department of Energy, the National Science Foundation, and the
National Institutes of Health.
I am eternally thankful for the love and support of my parents, my husband Liang,
my parents-in-law Suying and Xuexian, and the rest of my family. I especially want to
mention my ‘partner in crime’ Liang, who’s also a chemical engineering graduate student
at U-M, for being a constant source of motivation and support, and I look forward to
starting our next chapter in Boston. I want to express my gratitude to my parents for
always believing in me, respecting and supporting every decision I made. I’d also like to
acknowledge my parents in law for their endless support and making me always feel at
home. I want to thank my cousin in law Yun Li and her husband Jun Zhao for letting us
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crash at their place and treating us to delicious Chinese food every time we visit Seattle.
Last but not the least, I want to thank cat Meme for bringing joy and laughter to our life.
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TABLE OF CONTENTS

DEDICATION .................................................................................................................... ii
ACKNOWLEDGEMENTS ............................................................................................... iii
LIST OF FIGURES ............................................................................................................ x
LIST OF SCHEMES ..................................................................................................... xviii
LIST OF TABLES ............................................................................................................ xx
ABSTRACT .................................................................................................................... xxii
Chapter 1 Introduction .................................................................................................... 1
1.1 Background and Research Overview ........................................................................ 1
1.2 Sequence-controlled Polymers .................................................................................. 2
1.2.1 Synthetic Approaches to Sequence-controlled Polymerization ......................... 4
1.2.2 Nucleic Acids as Biological Sequence-controlled Polymers and DNA
Nanotechnology ........................................................................................................ 10
1.2.3 Sequence-specific Peptoids .............................................................................. 14
1.3 Dynamic Covalent Chemistry ................................................................................. 28
1.4 Dynamic Imine Chemistry and Its Emerging Applications .................................... 32
1.5 Covalent Self-assembly .......................................................................................... 40
1.6 Overview of Subsequent Chapters .......................................................................... 42
1.7 References ............................................................................................................... 43
Chapter 2 Dynamic Covalent Assembly of Peptoid-Based Molecular Ladders ....... 55
2.1 Original Publication Information ............................................................................ 55
2.2 Abstract ................................................................................................................... 55
2.3 Introduction ............................................................................................................. 56
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2.4 Experimental ........................................................................................................... 58
2.4.1 General Experimental Procedure ..................................................................... 58
2.4.2 Monomer Synthesis ......................................................................................... 59
2.4.3 Synthesis of Peptoids Bearing Dynamic Covalent Functionalities .................. 69
2.4.4 Cleavage and Side-chain Deprotection ............................................................ 70
2.4.5 Purification of Oligopeptoids by Preparative RP-HPLC ................................. 71
2.4.6 Characterization of Peptoids Bearing Dynamic Covalent Functionalities ...... 74
2.4.7 General Procedure for Self-assembly of Molecular Ladders of Length n ....... 83
2.5 Results and Discussion ........................................................................................... 84
2.5.1 Formation of Short Peptoid-based n-Rung Ladders (n = 3~6) ........................ 87
2.5.2 Formation of Long Peptoid-based n-Rung Ladders (n = 8~16) ...................... 90
2.6 Conclusions ............................................................................................................. 94
2.7 References ............................................................................................................... 95
Chapter 3 Reaction Kinetics and Registry Mechanism of n-Rung Molecular Ladder
Formation ........................................................................................................................ 99
3.1 Original Publication Information ............................................................................ 99
3.2 Abstract ................................................................................................................... 99
3.3 Introduction ........................................................................................................... 100
3.4 Experimental ......................................................................................................... 101
3.4.1 General Experimental Procedures .................................................................. 101
3.4.2 Experimental Procedures for Kinetics of Molecular Ladder Formation ....... 103
3.4.3 Synthesis and Characterization of DABCYL-EN for Subsequent Solid-phase
Peptoid Synthesis .................................................................................................... 104
3.4.4 Synthesis and Characterization of Oligopeptoids for FRET Study ............... 106
3.4.5 Photoluminescence Spectroscopy .................................................................. 112
3.5 Results and Discussion ......................................................................................... 113
3.5.1 Kinetics of Molecular Ladder Formation with n Rungs ................................ 113
3.5.2 Registry Mechanism of n × n Molecular Ladder Formation by Förster
Resonance Energy Transfer (FRET) ....................................................................... 121
3.6 Conclusions ........................................................................................................... 127
3.7 References ............................................................................................................. 129
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Chapter 4 Long, Self-assembled Molecular Ladders by Vernier Templating ........ 131
4.1 Original Publication Information .......................................................................... 131
4.2 Abstract ................................................................................................................. 131
4.3 Introduction ........................................................................................................... 132
4.4 Experimental ......................................................................................................... 134
4.4.1 General Experimental Procedure ................................................................... 134
4.4.2 Monomer Synthesis ....................................................................................... 135
4.4.3 Synthesis and Characterization of Peptoids for Vernier Templating and
Molecular Ladder Scrambling ................................................................................ 138
4.4.4 General Procedure for Vernier-templated Self-assembly of Molecular Ladders
of Length m × n ....................................................................................................... 141
4.4.5 Procedure for Dynamic Covalent Assembly of Ladder ME3A-Im_4 ............ 142
4.4.6 Procedure for Molecular Ladder Scrambling by Strand Exchange ............... 143
4.5 Results and Discussion ......................................................................................... 144
4.5.1 Vernier-templated Assembly of Complementary m×n Oligopeptoids .......... 144
4.5.2 Molecular Ladder Scrambling by Strand Exchange ...................................... 151
4.6 Conclusion ............................................................................................................ 156
4.7 References ............................................................................................................. 157
Chapter 5 In Situ Deprotection and Dynamic Covalent Assembly Using a Dual Role
Catalyst .......................................................................................................................... 158
5.1 Original Publication Information .......................................................................... 158
5.2 Abstract ................................................................................................................. 158
5.3 Introduction ........................................................................................................... 159
5.4 Experimental ......................................................................................................... 161
5.4.1 General Experimental Procedure ................................................................... 161
5.4.2 Monomer Synthesis ....................................................................................... 161
5.4.3. Solid-phase Synthesis of Oligo(peptoid)s ..................................................... 172
5.4.4 Amine Protecting Groups and Deprotection .................................................. 179
5.4.5 Deprotection of Acetal Group by Lewis Acids .............................................. 182
5.5 Results and Discussion ......................................................................................... 183
5.5.1 Orthogonal Protecting Groups for Amines and Aldehydes ........................... 183
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5.5.2 Optimization of Acetal Deprotection by Sc(III) ............................................ 188
5.5.3 Sc(III) as a Dual Role Catalyst ...................................................................... 195
5.5.4 Information-bearing Peptoids and Self-assembly of Complex Structures ..... 199
5.6 Conclusion ............................................................................................................ 207
5.7 References ............................................................................................................. 208
Chapter 6 Concluding Remarks and Future Directions ........................................... 211
6.1 Summary of Research ........................................................................................... 211
6.2 Future Work .......................................................................................................... 217
6.3 References ............................................................................................................. 221
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