Degree Type

Dissertation

Date of Award

2015

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Arthur H. Winter

Abstract

Part I. Self-immolative linkers are dynamic molecules which connect a cleavable mask to an output cargo molecule. Upon an input reaction that cleaves the mask, the self-immolative linker releases the output cargo. The scope of my research is synthesis of a new class of self-immolative linkers--aryl phthalate esters-sensitive to various inputs and able to release various cargo molecules, including within S2 cells.

In Chapter 1, fluoride sensitive aryl phthalate esters containing a phenolic output cargo molecule were synthesized. The fluoride sensitive 2-(trimethylsilyl)ethyl ether group was used as the mask molecule for each ester. The output cargo molecules were phenol, 7-hydroxycoumarin, and 3-(2-benzothiazolyl)-7-hydroxycoumarin. Full release of the cargo molecules were followed by NMR and fluorescence spectroscopy. The 7-hydroxycoumarin containing phthalate ester showed a 730-fold increase in fluorescence upon complete fluoride deprotection, making these compounds potential fluoride sensors.

In Chapter 2, self-immolative aryl phthalate esters conjugated with cleavable masking groups sensitive to light and hydrogen peroxide are reported. By altering the masking group, the phthalate linker releases the fluorescent dye 7-hydroxycoumarin upon exposure to stimuli such as light or hydrogen peroxide, respectively, leading to an increase in fluorescence. The light-sensitive aryl phthalate ester is demonstrated as a pro-fluorophore in cultured S2 cells.

Part II. BODIPY dyes can be meso-substituted to provide a new class of photoremovable protecting groups (PPGs). A PPG is the term used to describe a moiety (also known as a photocage) that has a deactivating influence on the biological substrate to which it is covalently attached. Once the covalent bond is broken, the substrate is released and its reactivity or function is regained. Ideally, the cage detaches only through the action of light, giving investigators precise temporal and spatial control.

In Chapter 3, photoremovable protecting groups derived from meso-substituted BODIPY dyes release acetic acid with green wavelengths >500 nm, and photorelease is demonstrated in cultured S2 cells. The photocaging structures were identified by our lab's previously proposed strategy of computationally searching for carbocations with low-energy diradical states as a potential indicator of a nearby conical intersection. The superior optical properties of these photocages make them promising alternatives to the popular o-nitrobenzyl photocage systems.

In Chapter 4, a meso-substituted BODIPY photoremovable protecting group from Chapter 3 has been red-shifted by extending the conjugation of the BODIPY structure using a Knoevenagel condensation reaction. Release of acetic acid from the BODIPY photocage is successful using >600 nm light, making these photocages promising for use in photorelease studies in whole tissues or animals.

DOI

https://doi.org/10.31274/etd-180810-4079

Copyright Owner

Kaitlyn M. Mahoney

Language

en

File Format

application/pdf

File Size

133 pages

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