Self-Assembly Using Alkene/Imine Orthogonal Dynamic Covalent Chemistry and Arylene

183 Pages·2017·6.18 MB·English

University of Colorado, Boulder
CU Scholar
Chemistry & Biochemistry Graduate Theses &
Chemistry & Biochemistry
Dissertations
Spring 1-1-2016
Self-Assembly Using Alkene/Imine Orthogonal
Dynamic Covalent Chemistry and Arylene-
Ethynylene Macrocycle/DNA Hybrids
Kenji D. Okochi
University of Colorado at Boulder, [email protected]
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Recommended Citation
Okochi, Kenji D., "Self-Assembly Using Alkene/Imine Orthogonal Dynamic Covalent Chemistry and Arylene-Ethynylene
Macrocycle/DNA Hybrids" (2016).Chemistry & Biochemistry Graduate Theses & Dissertations. 185.
https://scholar.colorado.edu/chem_gradetds/185
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Self-Assembly Using Alkene/Imine
Orthogonal Dynamic Covalent Chemistry and
Arylene-Ethynylene Macrocycle/DNA Hybrids
by
Kenji D. Okochi
B.S. Tulane University, New Orleans, LA, 2007

A thesis submitted to the
Faculty of the Graduate School of the
University of Colorado in partial fulfillment
of the requirement for the degree of
Doctor of Philosophy
Department of Chemistry and Biochemistry
2016
This thesis entitled:
“Self-Assembly Using Alkene/Imine Orthogonal Dynamic Covalent Chemistry and
Arylene-Ethynylene Macrocycle/DNA Hybrids”
written by Kenji D. Okochi
has been approved for the Department of Chemistry and Biochemistry

______________________________________
Wei Zhang, Ph. D.

______________________________________
David Walba, Ph. D.

Date__________________________

The final copy of this thesis has been examined by the signatories and we
find that both the content and the form meet acceptable presentation standards
of scholarly work in the above mentioned discipline.
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Thesis Abstract
Okochi, K. D.
(Ph.D., Department of Chemistry and Biochemistry)
Self-Assembly Using Alkene/Imine Orthogonal Dynamic Covalent Chemistry and
Arylene-Ethynylene Macrocycle/DNA Hybrids
Thesis directed by Professor Wei Zhang

The controllable assembly of materials on the atomic or molecular level remains
one of the grand challenges of chemistry. While top-down techniques such as
lithography are capable of creating order over the long range, short range assembly on
the order of up to 10 nanometers is currently beyond the scope of the most advanced
lithographic capabilities. Self-assembly using bottom-up strategies have the potential to
fill in this void, and there remains a fundamental need to have multiple strategies for
the creation of materials at this scale. Herein we present research focusing on two areas
of self-assembly: Alkene/imine ODCC and arylene-ethynylene macrocycle/DNA
hybrids that can mediate assembly of gold nanoparticles.
Dynamic covalent chemistry (DCvC) is one technique available to chemists to
synthesize matter in a controllable manner using bottom-up assembly. However, to
date, the majority of DCvC reactions rely on one type of chemistry (homo-sequenced),
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resulting in structures with high symmetry. In contrast, the incorporation of two types
of DCvC (hetero-sequenced) into one reaction has been relatively less explored. We
first demonstrated that alkene metathesis and imine metathesis DCvC can be utilized in
a one-pot fashion to synthesize discrete 2-D phenylene-based macrocycles. Next we
showed that macrocycles made in this manner could form a 1-D polymer of
macrocycles using alkyne metathesis DCvC and also prepare 3-D and 3-component
shape-persistent architectures from simple building blocks.
Organic/DNA hybrids offer the potential for material whose self-assembly
properties are imparted both by the hydrophobicity and directionality of the organic
component as well as the base-pairing capabilities of the DNA. While most research
has focused on either small molecule/DNA hybrids or polymer/DNA hybrids, discrete
oligomeric architectures provided by DCvC such as arylene-ethynylene macrocycles,
offer an intriguing intermediate hybrid that could be incorporated into gold
nanoparticle lattices for plasmonic applications. We first explored the synthetic
conditions of the on-bead amide coupling using a small library of simple organic
substrates and achieved good yields. Next we demonstrated that arylene-ethynylene
macrocycle/DNA hybrids can be prepared using the methodology we had developed
for small molecules, and that the resulting macrocycle/DNA material can be used to
assemble gold nanoparticles into both bulk aggregates and discrete assemblies of
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dimers depending on the DNA sequence; complementary sequences yielded bulk
aggregates, while poly-adenines yielded dimers.

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DEDICATION

Dedicated to my collaborators

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Acknowledgements
I would first like to thank Prof. Wei Zhang for his leadership and vision. Wei’s
high standards of scientific rigor has made me a much better scientist than I would
otherwise be, and I am grateful for having him as an advisor. I would like to thank my
fellow members of the Zhang group who I have had the pleasure of working with over
the past six years: Yinghua (Alice) Jin, Ryan McCaffrey, Youlong Zhu, Chao Yu,
Michael Ortiz, Chengpu Zhu, Yu Gong, Shouhong Fan and David Tran. I would also
like to thank past members of the Zhang group: Jyothish Kuthanapillil, Chenxi Zhang,
Qi Wang, Philip Taynton, Ya Du, Ryan Denman, Athena Jin, Guolong Lu, Lili Tan, Kun
Xun, Prof. Dazhi Tan, and Prof. Huagang Ni. I would especially like to thank Dr.
Haishen Yang for his guidance in helping me become a better chemist. In my time at
CU Boulder, I have had the opportunity to work with a number of hard-working
undergraduates: Gun Han, Ian Aldridge, Yuliang Liu, and Alex Herron, thank you guys
for your help.
I have been very fortunate in that I have been able to work with high caliber and
helpful collaborators. While most Ph.D. students are a member of one or two groups, I
feel like I have been part of at least four groups in my time here due to my
collaborations. I wish to thank Prof. Jennifer Cha, Prof. Marvin Caruthers, and Prof.
Robert Kuchta for allowing me to collaborate with their students and post-docs. I
would particularly like to thank Prof. Dylan Domaille, Dr. Luca Monfregola, Sarah
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Dickerson, and Ryan McCaffrey for their time, energy, patience and expertise on the
DNA project. I’d also like to thank Prof. Daniel Feldheim and Prof. Bruce Eaton for
letting me use their lab equipment.
I wish to thank my family, my parents, Andy and Nancy, and my sisters Mina
and Rena for supporting me throughout my life. Most of all I wish to thank my
wonderful wife, Christine, who has put up with my crazy hours and work schedule to
somehow keep our home standing, particularly with the addition of our twin
sons/DNA hybrids, Andrew and Bryant (1/26/16).
I wish to thank the National Science Foundation for financial support as well as
the University of Colorado Boulder and the Department of Chemistry and
Biochemistry.

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CONTENTS
CHAPTER 1 ..................................................................................................................................1
1.1 Introduction .........................................................................................................................1
1.2 Orthogonal dynamic covalent chemistry .........................................................................3
1.3 Organic/DNA hybrids .......................................................................................................7
1.3.1 Solution-phase convergent ........................................................................................10
1.3.2 Solid-state divergent ..................................................................................................14
1.3.3 Solid-state convergent ................................................................................................17
1.4 Conclusion .........................................................................................................................19
1.5 Scope of thesis ...................................................................................................................20
1.6 Organization of thesis ......................................................................................................20
1.7 References ..........................................................................................................................21
CHAPTER 2 ................................................................................................................................24
2.1 Introduction .......................................................................................................................24
2.2 Model studies .....................................................................................................................25
2.3 Synthesis of ODCC monomers ........................................................................................28
2.4 Alkene/imine ODCC ........................................................................................................30
2.4.1 ODCC macrocyclization trial 1 .................................................................................30
2.4.2 ODCC macrocyclization trial 2 .................................................................................32
2.4.3 ODCC macrocyclization trials 3 and 4 ....................................................................34
2.5 Asymmetric macrocycles ................................................................................................38
2.6 Polymers of ODCC macrocycles ....................................................................................41
2.6.1 Synthesis of ODCC macrocyclic monomers ...........................................................41
2.6.2 ODCC macrocyle aggregation study .......................................................................45
2.6.3 ODCC macrocyclization study .................................................................................46
2.6.3.1 Polymerization by alkyne metathesis ..............................................................48
2.6.3.2 Polymerization by Glaser coupling ..................................................................48
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