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Structural variation in π-conjugated DNA binders through click chemistry: synthesis and interaction studies

Althagafi, Ismail 2012. Structural variation in π-conjugated DNA binders through click chemistry: synthesis and interaction studies. PhD Thesis, Cardiff University.
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Abstract

This thesis presents the design, synthesis and physical studies of new structurally-varied cationic oligoheteroaromatic DNA binders in six chapters. Chapter 1 introduces DNA and its importance in modern science such as genetic and medicinal research. The interactions of DNA with small molecules are also discussed. A description is provided of click chemistry, a method for the synthesis and design of structurally-varied molecules, in this case designed to interact with DNA. Chapter 2 presents the synthesis of alkyne-substituted oligoheteroaromatic compounds by means of bromination, iodination, and Suzuki, Stille and Sonogashira cross-coupling reactions. These alkyne-substituted oligoheteroaromatic compounds were designed to be used as building blocks for click reactions. Chapter 3 describes the synthesis of azide-substituted oligoheteroaromatic compounds from amines by means of a safe method. The Pd-catalysed cross-coupling of azidesubstituted building blocks to form oligoheteroaromatics is also described. The azidesubstituted oligoheteroaromatic compounds were designed as building blocks complementary to the alkyne-substituted compounds described in Chapter 2. Chapter 4 presents the synthesis and characterisation of new π-conjugated molecules utilising click chemistry between alkyne- and azide-substituted compounds leading to a series of structurally-varied di- and tricationic oligoheteroaromatic putative DNA binders. Chapter 5 describes DNA-binding studies for the di- and tricationic oligoheteroaromatic compounds using a variety of biophysical techniques to quantify DNA binding and elucidate binding modes. Additionally, this chapter presents results from preliminary V exploration of the sequence selectivity of our cationic oligoheteroaromatics by comparing binding affinities and binding modes for two different sequences of DNA, viz. poly(dGdC)40 and poly(dA)80poly(dT)80. Chapter 6 presents the preliminary synthetic and DNA-binding studies of selected extended cationic oligoheteroaromatic compounds. Finally, this chapter presents the overall conclusions of the study, including selected comments and suggestions about future studies and applications.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:11
URI: http://orca.cf.ac.uk/id/eprint/41968

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