Characterization and Synthesis of Cyclodextrin Inclusion Complexes and their Applications as Fluorescent Probes for Sensing Biomacromolecules

• Main Author: Gomez Biagi, Rodolfo F.
• Other Authors: Nitz, Mark
• Language: en_ca
• Published: 2012
• Subjects: Cyclodextrin; Chemistry; 0490
• Online Access: http://hdl.handle.net/1807/34016

Cyclodextrins (CDs) are macrocycles composed of several glucose units bound through α-1,4 glycosidic linkages. They can be chemically modified to display functional groups on their primary or secondary rim. CDs display these groups in defined geometries ideally suited to bind biomacromolecules. Moreover, CDs have a hydrophobic cavity that allows them to form stable host-guest complexes with lipophilic molecules. This combination of functionality and guest binding ability makes CDs important scaffolds for the design of functional supramolecular systems. This thesis explored the interaction of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-cyclodextrin (1) with many hydrophobic guest molecules. The binding constants of CD host-guest interactions were measured using ITC and fluorometry-based approaches. These studies revealed 1 to form the highest affinity 1:1 cyclodextrin-guest complexes reported to date. This thesis then explored the use of CD inclusion complexes as biomacromolecular sensors. CD 1 and its derivatives were used to develop self-assembling sensors. First, a library of polycationic CDs with differing charge distribution was synthesized. The sensing motif was synthesized by covalently linking a quinolinium fluorophore to lithocholic acid (LCA). The CD-based binding motifs and the LCA-based sensing motif self-assemble through host-guest interactions (i.e. 1 binding to LCA displays a Ka = 5.52 × 107 M-1). These inclusion complexes were then used as an array of self-assembling sensors capable of differentiating between pure and contaminated samples of heparin (anticoagulant). To capitalize on the promise of CD 1 a new technique was explored to functionalize a single amine of 1. The technique relies on an S to N acyl transfer from a guest molecule to a CD host resulting in the mono-acylation of the host. The importance of the linker between the guest and the reactive acylating agent was fully explored. Furthermore, two CD probes are synthesized and are shown to display differential fluorescent responses with a small series of proteins.