Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

David M. Chenoweth

Abstract

Natural products have been a valuable source of inspiration for organic chemists, both as synthetic challenges and as potential candidates for drug development or other biological applications. Xylopyridine A, a nucleic acid binding natural product, had an intriguing reported structure with a potentially unique mode of intercalation. We have designed its synthesis and successfully obtained the reported structure; however, nucleic acid binding studies of the molecule itself could not be carried out due to insolubility. Despite this, the monomethylated derivative was water soluble and showed remarkable selectivity toward G-quadruplex nucleic acid structures. The derivative also possessed great potential as a cellular stain for fluorescent cell imaging due to its large Stokes shift, high water solubility, low cytotoxicity, high selectivity toward lysosomes, and the capability of in-cell photoconversion. Regioisomers of the derivative were synthesized, one of which has shown similar properties with higher photostability and selectivity to mitochondria. Many other derivatives of the reported structure of xylopyridine A were also made and hold great potential for use as fluorescent cellular dyes for both live and fixed specimens with good photoproperties, cell permeability, and high resistance to photobleaching.

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