Dissertation/Thesis Abstract

Investigating the Relationship Between Structure and Self-Assembling Behavior of Fmoc-Protected Phenylalanine Derivatives
by Rajbhandary, Annada, Ph.D., University of Rochester, 2016, 380; 10179025
Abstract (Summary)

Low molecular weight (LMW) hydrogelators have been utilized for numerous biomedical applications in cell culture, drug delivery and tissue engineering. Fluorenylmethoxycarbonyl (Fmoc) protected phenylalanine (Fmoc-Phe) derivatives are a privileged class of LMW hydrogelators that have excellent gelling abilities and have found uses in various functional applications. Since a large number of LMW hydrogelators have been discovered serendipitously, further understanding of the molecular structure and conditions that drive self-assembly and hydrogelation processes is imperative for intelligent design of biomaterials. This thesis investigates the structural differences of molecules which facilitate various types of self-assembly and hydrogelation processes. The first project investigates new ways of forming hydrogels by simple dissolution in water. While most gelling processes either rely on toxic organic co-solvents or stringent pH conditions to induce hydrogelation, our investigated method of forming hydrogels in unbuffered water in the absence of harsh condition, is comparatively more biocompatible for uses in cell culture applications. We utilized a cationic Fmoc-Phe based hydrogelators that can form gels in water upon addition of salt. These hydrogelators also form homogenous nanotubes at high gel concentrations which are exclusively dependent on the presence of the cationic charges. In the second project, we investigated the importance of hydrogen bonding in LMW gelators in giving directionality to the one-dimensional (1D) fibrils. Self-assembly behavior of amino acid and peptoid derivatives of Fmoc-phe monomers were compared. It was found that while amino acid monomers prefer formation of one-dimensional (1D) fibrils, peptoid monomers prefer forming two-dimensional (2D) sheets in the absence of hydrogen bonds. Crystals of the variants were obtained in different solvent-water conditions which were analyzed via X-ray diffraction (XRD). The XRD data revealed stark differences in packing arrangements of Fmoc-Phe amino acid and peptoid monomers. Amino acid monomers preferred parallel π–π stacking whereas most peptoid monomers displayed antiparallel and intramolecular π–π stacking. Finally in the third project, we investigated the self-assembly behavior of peptide/peptoid hybrids of the most widely studied dipeptide, Fmoc-Phe-Phe to understand it’s self-assembly propensity in the absence of hydrogen bonds and changes in the spatial arrangement of side chains. Hybrid peptide/peptoid variants were able to self-assemble even in the presence of only single hydrogen bond although fibrillization was not possible in the absence of both hydrogen bonds. Although self-assembly of the hybrid variants to form fibrils was possible, the gelling ability of these variants were greatly reduced mostly due to the stark differences in the hydrogen bonding abilities and spatial arrangement of the side chains. Therefore, with the research work presented in this thesis, insight into understanding of the structural and spatial arrangement of molecules that lead towards self-assembly and hydrogelation was obtained. This knowledge can be applied in future for intelligent design of materials with varied functional applications.

Indexing (document details)
Advisor: Nilsson, Bradley L.
Commitee: Fasan, Rudi, Goldfarb, David S., Krugh, Thomas R., White, Andrew
School: University of Rochester
Department: School of Arts and Sciences
School Location: United States -- New York
Source: DAI-B 78/03(E), Dissertation Abstracts International
Subjects: Chemistry
Keywords: Bioorganic chemistry, Phenylalanine derivatives
Publication Number: 10179025
ISBN: 9781369291407
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