BORON-BASED AND ORGANOMETALLIC LUMINESCENT SCAFFOLDS FOR NUCLEIC ACID RECOGNITION AND PH PROBING
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Authors
Novoseltseva, Polina
Date
Type
thesis
Language
eng
Keyword
Luminescence , pH probe , BF2 beta-diketonates , Platinum(II) , Guanine quadruplex
Alternative Title
Abstract
In this thesis, luminescence is imparted to molecules designed to perform pH sensing, drug delivery and guanine quadruplex binding. For pH sensing and drug delivery, luminescent pH-responsive molecular scaffolds were developed on the basis of BF2 ß-diketonates, some of which exhibit a conformational switch upon H+ binding. For the purposes of guanine quadruplex binding, a phosphorescent Pt(II) complex with N^C^N ligand core was constructed. Each with a unique design, the two molecule families are linked by a common end-goal: to visualize key biological processes upon future implementation in vivo.
Chapter 2 is centered around a family of new aromatic BF2 ß-diketonates and their properties in the context of pH sensing and drug delivery applications. First, the synthesis, purification, and characterization each BF2 ß-diketonate are described at length. Next, the pH-responsive nature of pyridine-containing BF2 ß-diketonates and their conformational switching ability upon H+ binding are established by 1H NMR and 1D NOESY spectroscopies following incremental acid addition. The changes observed in absorption and emission of BF2 ß-diketonates upon H+ binding in acetonitrile are also described and rationalized with the help of TD-DFT computation. Finally, the stability of some of the synthesized BF2 ß-diketonates is modeled by assessing their emission in aqueous environments of varying pH (DI water, pH 2 PBS, pH 5 PBS, pH 8 PBS) over extended periods of time. The obtained results are discussed in the context of their pH sensing and drug delivery potential.
In Chapter 3, the unique features of a new Pt(II)-based intrinsically luminescent guanine quadruplex binder, a Pt-dqb(Cl) complex, are described in detail (dqb = 4-methylamine-2,6-di(2- quinolyl)benzene). To achieve the synthesis of this complex, four synthesis routes (Route 1 to 4) are proposed, and Routes 1 and 2 explored. Of the two, synthesis via Route 2 was found to be more promising, giving the oxime-protected dqb ligand at an overall yield of 16%. To circumvent the moisture sensitivity of the coupling reaction employed in Route 2, alternative Routes 3 and 4 are proposed for future synthesis attempts.
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Attribution-NonCommercial-NoDerivs 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivs 3.0 United States