Rahul Prakash

Date of Award

Fall 2023

Document Type

Open Access Dissertation


Chemistry and Biochemistry

First Advisor

Linda Shimizu


This dissertation is divided into two topics: I. Supramolecular polymerization of triphenylamine (TPA) bis-urea macrocycle behavior in solution, and II. Synthesis of fluorophore appended and biotinylated derivatives of NSC243928 for the treatment of triple-negative breast cancer. Supramolecular polymers are of interest due to their self-healing and stimuli responsiveness. Chapter 1 gives a brief overview of the importance of self-assembly to construct ordered structures from smaller building blocks, highlighting the mechanisms of self-assembly to form supramolecular polymers. The bis-urea macrocycle assembly unit is introduced and its assembly into tubular structures and crystals is highlighted, which are used as a control for subsequent studies. Chapter 2 explores the cooperative self-assembly of a dendronized triphenylamine (TPA) bis-urea macrocycle to afford supramolecular polymers. This macrocycle demonstrates concentration and temperature-dependent aggregate formation in both THF and H2O/THF mixtures. This phenomenon is illuminated through a wide array of spectroscopic and microscopic techniques. Additionally, the impact of guest molecules, such as diphenylacetylene, and chain stoppers, such as diphenyl sulfoxide, on the elongation of these assemblies is unveiled. This underscores the potential of tailoring the macrocycle's function through strategic selection of (co)monomers. Chapter 3 extends these investigations of the TPA bis-urea macrocycle assembly to toluene solutions, where it shows remarkable gelation. Classified as a super-gelator, it exhibits thermoreversible gel-sol phase transitions, which are meticulously detailed. Rheological experiments contribute valuable insights into its mechanical properties, with a particular emphasis on its self-healing capabilities. Furthermore, the introduction of chain stoppers, namely dimethyl sulfoxide (DMSO) and diphenyl sulfoxide (DPS), leads to the formation of weaker gels and partial recovery. Chapter 4 turns towards the synthesis of NSC243928 along with its fluorophore appended and biotinylated derivatives. NSC243928 is a promising therapeutic target for triple-negative breast cancer. The direct affinity of the newly synthesized derivatives of NSC243928 for the LY6K protein is confirmed by surface plasmon resonance (SPR) assays. In addition, confocal microscopy studies show retention of the fluorophore derivative within LY6K-expressing cancer cells. Finally, Chapter 5 consolidates key findings and outlines future avenues of exploration and potential applications. It represents a significant contribution to the fields of supramolecular chemistry and cancer research.


© 2024, Rahul Prakash

Available for download on Tuesday, December 31, 2024

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