Dissertation
Making molecules in crystals: photo-responsive gold(i) macrocycles, cubane-like cages, and rapid product diversification
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2022
DOI: 10.25820/etd.006661
Abstract
Controlling reactions in crystalline solids provides new opportunities in synthetic chemistry and materials science. Much effort has been devoted to using non-covalent interactions (e.g., hydrogen bonding, halogen bonding and metal coordination) to direct the formation of covalent bonds in photoactive solids. In this case, use of small organic molecules (e.g., resorcinols) as templates to assemble reactants (i.e., olefins) in a desired geometry for a [2+2] photodimerization continues to draw research interest. While tremendous progress has been made in the field during the past two decades, additional studies are essential to expand the toolbox of non-covalent interactions to enable the design and synthesis of functional solid materials as well as structurally diverse molecular building blocks. Moreover, achieving single-crystal-to-single-crystal (SCSC) reactivity and rapid functional group diversification of the photoproduct remains challenging.
The dissertation addressed the challenges using principles of supramolecular design and crystal engineering strategies. In doing so, aryl nitriles, one of most versatile functional groups in organic synthesis, were introduced to serve a dual role as both hydrogen-bond-acceptors and modifiable organic functional groups. The programmable design was realized by preparing a bis(aryl nitrile) alkene that self-assembles with resorcinol by hydrogen bonding to form a photoreactive solid. The pre-organized bis(aryl nitrile) alkene went through an intermolecular [2+2] photodimerization to afford a tetra(aryl nitrile)cyclobutane stereoselectively and in 100% yield. The product is readily convertible to a tetra(aryl tetrazole) via click reactivity and a tetra(aryl carboxylic acid) via hydrolysis. We expect the reported method to pave the way for post-modifying products formed in crystalline solids for rapid diversification.
As part of our efforts to synthesize structurally diverse molecular architectures, highly-symmetric cubane-like cages were synthesized stereoselectively and in quantitative yield through double [2+2] photodimerizations. A tetraacid cubane-like cage was constructed from a photodimerization of one of the cyclic dienes in cocrystal components. The second cyclic diene, while photostable in the cocrystal, reacts as a pure form quantitatively to form a tetramethyl cubane-like cage. In addition to three-dimensional (3D) organic cages, we fabricate one-dimensional (1D) DNA-like bundles and 3D networks in small-molecule drug-drug cocrystals. Specifically, cocrystals composed of antiretroviral drug lamivudine and cytotoxic chemotherapy drug 5-fluorouracil was synthesized in 1:1 and 1:2 ratios. The components of the cocrystals self-assemble through unusual pyrimidine⋯pyrimidine base pairing between the cytosine (C) ring of the non-phosphate nucleoside analog lamivudine and the uracil (U) base of the nitrogenous base analog 5-fluorouracil to form DNA-like supramolecular architectures.
Non-covalent interactions lie at the core of supramolecular chemistry and crystal engineering. In this context, we integrated gold(I) coordination and aurophilic interactions to design and synthesize photoreactive tetranuclear gold(I) macrocycles. Within the metal-organic complex, C=C bonds are arranged in a favorable geometry for a photodimerization reaction. The photoreaction proceeds via a rare SCSC transformation that retains the crystallinity. The single-crystal reaction generates photoproduct stereoselectively and quantitively with new ramp-like features on the surfaces of single crystals. Additionally, we used a less common type of hydrogen bond in the form of N+-H···N to support a cascade-like [2+2] photodimerization in a salt cocrystal. The charge-assisted hydrogen bond and cation···π interaction sustain the formation of photoactive ionic assemblies that undergo a SCSC transformation to give cyclobutane product in head-to-tail (ht) orientation. The photodimerization of ionic assemblies rearranged the molecular geometry of the photostable assemble to become photoreactive. The outcome is the regiocontrolled formation of cyclobutane product in 100% yield.
Details
- Title: Subtitle
- Making molecules in crystals: photo-responsive gold(i) macrocycles, cubane-like cages, and rapid product diversification
- Creators
- Changan Li
- Contributors
- Leonard R MacGillivray (Advisor)Scott R Daly (Committee Member)F Christopher Pigge (Committee Member)Scott K Shaw (Committee Member)Alexei V Tivanski (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Autumn 2022
- DOI
- 10.25820/etd.006661
- Publisher
- University of Iowa
- Number of pages
- xvii, 170 pages
- Copyright
- Copyright 2022 Changan Li
- Language
- English
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 120-152).
- Public Abstract (ETD)
In the physical sciences there are three states of matter: solid, liquid, and gas. Organic chemistry is typically performed in the liquid or solution phase. This dissertation aims to advance the solid state as a medium to perform chemical reactions. The solid state is solvent free and therefore is beneficial for performing reactions that do not contribute to waste in the environment. However, the rules to perform reactions in organic solids are not clear and this work contributes to the formation of such rules.
Specifically, we describe a method that allows to reliably perform reaction in crystals. The method uses “templates” to “shepherd” reactant molecules in a desired position for creating new molecules. Weak attractions between template and reactant have proven successful in achieving the desired arrangement. By shining UV-light on the solids, useful molecules in the shape of rings or cages can be easily produced. Additionally, we introduce an organic functional group as a “tag” for molecular recognition and chemical modification, providing access to a diverse range of molecules with interesting structures and functions. We also make functional materials including gold-containing crystals that respond to light. The discoveries presented in the dissertation provide clearer rules to allow reactions to be performed in organic crystals and, ultimately, benefit the planet.
- Academic Unit
- Chemistry
- Record Identifier
- 9984362558402771
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