Revealing DNA’s secret structures: development of an i-Motif specific ruthenium-based probe

Spence, Philip (2020) Revealing DNA’s secret structures: development of an i-Motif specific ruthenium-based probe. Doctoral thesis, University of East Anglia.

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Chapter 1 is general introduction to DNA and the secondary structures that it forms, leading into an introduction to ruthenium-based polypyridyls and their application as secondary structure probes.

Chapter 2 discusses the DNA interactions of mer-, trans,fac-, and cis,fac-[Ru(bqp)2]2+. This explores the photophysical changes that occur upon DNA binding and the discovery that the cis,fac- isomer behaves as a light switch with DNA. It explores the specificity of this isomer and its two enantiomers (∆ and Λ) to i-motif DNA. This culminates in a hypothesis for the unique light switching mechanism caused by the steric and electronic interactions with DNA, rather than solvent exclusion.

Chapter 3 explores the synthesis of various bqp analogues. Here the discovery of a new synthetic route for the high yielding synthesis of cis,fac-[Ru(bqp)2]2+ that also enables the synthesis of heteroleptic bqp complexes, is also discussed, as well as the application of this synthetic route to the synthesis of facial bqp-containing complexes that incorporate metals other than ruthenium.

Chapter 4 discusses the results of a high-throughput screen using in silico and biophysical techniques with a library of 1584 molecules and an i-motif forming DNA sequence. The correlations between these three techniques is discussed as well as identification of the hits that are produced by each one.

Chapter 5 summarises Chapters 2, 3 and 4, and explores the future work that this project could take.

Chapter 6 describes the experimental procedures used in Chapters 2, 3 and 4.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Chris White
Date Deposited: 21 Apr 2021 11:45
Last Modified: 31 Jul 2023 01:38


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