Effects of epigenetic modification and ionic liquid on DNA charge transport : applications in biology and material

• Main Author: Xuan, Shuguang
• Other Authors: Shao Fangwei
• Format: Theses and Dissertations
• Language: English
• Published: 2016
• Subjects: DRNTU::Science::Chemistry
• Online Access: https://hdl.handle.net/10356/65990
• Institution: Nanyang Technological University

The well-aligned base pairs along the DNA central axis serve as a convenient pathway for charge migration. The phenomena termed as DNA charge transport (CT) has stirred up great interests about the underlining mechanism, biological roles and potential applications in development of DNA based electronic devices. Mechanistic investigations have revealed that various factors might affect the process of DNA CT, including inherent factors, such as the base pairs composing the "bridge" for charge migration, secondary structures and sequences of duplex DNA; and external factors, such as protein binding, external magnetic fields and solvents. The biological significance of DNA CT has been found to be associated with several redox processes in cell, such as funnelling oxidative stress, and signalling between proteins. On the other hand, applications of DNA CT in molecular electronics have been extensively studied to develop multi-functional DNA electronic devices. Despite the great achievements of previous studies with regards to DNA CT, further research is demanded to advance DNA CT to a higher step in its application biology and material. This thesis explored via two approaches: modulating DNA CT by epigenetic modification on base pair stacks and facilitating DNA CT by using hydrated ionic liquid as solvents. The attempts here provide critical progress in understanding biological functions of DNA CT and developing protocols to make DNA a better conductive biomaterial. Chapter 1 reviewed the current mechanisms for DNA mediated CT and the implications in biology and DNA based electronic devices. The effects of epigenetic modifications and ionic liquid on nucleic acids including structures, stability and biofunctions were also reviewed here. Chapter 2 reported facile syntheses of DNA oligonucleotides containing hmC and fC. With microwave assisted heating, commercial available nucleoside dT and mdC were readily oxidized to hmdU and fdC which were the key intermediates for hmC and fC phosphoramidites syntheses. The protocols established were applied for preparation of DNA sequences for study of epigenetic effects on DNA CT. Chapter 3 investigated a critical epigenetic process in active DNA demethylation, i.e. spontaneous deamination of epigenetic cytosines. Alkali treatment induced substantial spontaneous deamination of dC, mdC and hmdC at 37 ºC, however, converted fdC into two unknown moieties other than the corresponding deamination product fdU. Kinetics study of deamination reaction revealed spontaneous deamination rate of dC, mdC and hmdC was associated with the C5 functionality of cytosine pyrimidine ring. Effects of epigenetic modification on DNA CT were examined in chapter 4. Transient hole density during DNA charge transport was found to be modulated by various epigenetic cytosine modifications; oxidative G damage by DNA charge transport over long range was facilitated by hyper-methylation and inhibited by hmC and fC. Chapter 5 reported adopting hydrated ionic liquid as solvent to enhance charge transport through DNA. Striking increment of charge transport efficiency was observed with the presence of ionic liquid. The effects of water, ionic liquid cation and anion species, as well as binding of ionic liquid to DNA, were investigated in detail.