Date of Award

6-1-2012

Document Type

Thesis

Degree Name

M.S.

Department

Chemistry and Biochemistry

First Advisor

Byron W. Purse, Ph.D.

Keywords

Fluorescent nucleoside, Photophysical properties, tC8OMe, tC7OMe, tC nucleoside analogues

Abstract

This project aimed to obtain a set of fluorescent nucleoside analogues that closely resemble cytosine with extending the aromatic surface (extended conjugation) for enhance the photophysical properties. In addition to synthesize new fluorescent nucleoside analogues and evaluate their photophysical properties, this project aimed to understand the effects of donor substituent on the tC photophysical properties.

The main goal of these studies is to develop highly fluorescent nucleotide analogues. We first were looking to synthesize tCC fluorescent nucleotide with the pyrimido[4,5-b]quinolone. In this part, 2-chloro-3- formylquinoline was easily prepared, yet the cyclization of 2-chloro-3- formylquinoline with urea or guanidine HCl was the most challenging that faced us. However, we have synthesized 2-amino [4,5-b]quinoline-one ring tCC under super dry reaction conditions in <10% yield.

The second goal was synthesizing new modified fluorescent nucleoside derivatives of tricyclic cytidine, which structurally mimics natural cytidine, and evaluates the photophysical properties of the new fluorescent tC nucleoside to understand the affects of the donor substituent, OCH3, group on tC. In this part, we have reported new tC nucleoside derivatives with electrons donor substituent OCH3 group at carbon 7, tC7OMe, and the other at carbon 8, tC8OMe. These different substitution positions offer important distinctions between the design of the tC, tC8OMe, and tC7OMe. The unsubstituted tC nucleoside was easy to synthesize. In contrast, the synthetic strategy of the tC7OMe nucleoside that has electron donor substituent group OCH3 located at carbon 7 and para to amino group is synthetically less challenging and higher yielding than synthesis of tC8OMe which has OCH3 group substituent meta to amine group. Moreover, the photophysical properties of the fluorescent nucleoside derivatives of tC have been evaluated. Fluorescence studies of modified tC nucleosides demonstrated distinguish fluorescence emission and absorption wavelengths for tC7OMe, and tC8OMe, which displayed higher quantum yields and brightness compared to unmodified tC, dependent on mismatch position of the electron donor group (7 or 8) on the tC. This can be explained by the fact that the donor group OCH3 which allow for extended conjugation of unshared pairs of electrons lead to increases the freedom of the -electrons and likely to raise the fluorescence. Also, our fluorescence study established that there are effects of the different positions of substituent donor group. The fluorescence emission wavelength of tC8OMe, where the OCH3 is meta to amino group, is red sifted longer than the fluorescence emission wavelength of tC7OMe, where the OCH3 is para to amino group; however, tC7OMe exhibited higher quantum yield and brightness than tC8OMe.

Provenance

Received from ProQuest

Rights holder

Nada Abdulnasir Elsharif

File size

135 p.

File format

application/pdf

Language

en

Discipline

Organic chemistry, Chemistry

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