Date of Completion

2018

Document Type

Honors College Thesis

Department

Chemistry

Type of Thesis

College of Arts and Science Honors, Honors College

First Advisor

Dr. Severin T. Schneebeli

Second Advisor

Dr. Matthias Brewer

Third Advisor

Dr. Nathan J. Jebbett

Keywords

dynamic covalent chemistry, hydrazone-linked molecular cage, hydrogen bonding, supramolecular binding, solid-state isomerizations

Abstract

The field of supramolecular chemistry has enabled organic chemists to construct molecules of higher order complexity based on both covalent and noncovalent interactions. Receiving inspiration from biochemical systems, supramolecular chemistry has also been termed “chemistry beyond the molecule” because of its dominant use of interactions beyond the covalent bond, such as H-bonding, crystal packing, π–π stacking, metal coordination, halogen bonding, hydrophobic interactions, and the like[1]. Some examples of the chemical structures that became possible to synthesize by employing supramolecular strategies are macrocycles (e.g. cyclodextrins, crown ethers, calixarenes), mechanically interlocked molecular architectures (e.g. rotaxanes), molecular cages (e.g. metal–organic polyhedral), and so forth[2]. This thesis work was focused on the efficient synthesis of purely organic D3h cage linked through hydrazone (R1R2C=NNH2) functionality. A novel cage was constructed using dynamic covalent chemistry approach and hydrogen bond facilitated self-assembly in 95% yield. The design of the building blocks for this dimeric hydrazone-linked cage was tailored to be water-compatible and allow interactions with biologically significant guests, such as α-crocin, a carotenoid pigment found in saffron[3]. The binding constant of the cage with crocin was determined to be (3.2 ± 0.2) x 102 M–1 at 298 K with the 2:1 crocin: Dim-1 stoichiometry. The potential applications of this hydrazone-linked cage for supramolecular catalysis, biosensor development and drug delivery are part of current and future investigations. During the synthesis of the cage product, an interesting stereochemical behavior of the cage vertex precursor, syn-3, was also investigated. This compound existed as a mixture of atropoisomers in the solution but was amplified to a single stereoisomer by crystal-packing driven solid-state enrichment method developed by us[4]. The method of crystal-packing enrichment was extended to another complex mixture of atropoisomers leading to successful amplification of a minor atropoisomer. Both parts of this thesis work demonstrate how supramolecular interactions, ubiquitous in biological systems, could be applied in organic synthesis for generation of three-dimensional cages and analysis of the stereochemical behavior.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Wednesday, May 13, 2020

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