DNA-Mediated Hole and Electron Transport

Citation

Shao, Fangwei (2008) DNA-Mediated Hole and Electron Transport. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/VZ0J-W403. https://resolver.caltech.edu/CaltechETD:etd-06282007-105808

Abstract

Since the elucidation of the double helical structure of DNA, it has been proposed that the dynamic [pi]-stacking base pair array may mediate charge migration, hole transport (HT), and electron transport (ET). In this thesis work, both DNA-mediated HT and ET are investigated to explore their mechanisms by using kinetically fast electron/hole traps: cyclopropylamine-substituted bases, especially N₄-cyclopropylcytosine (^CPC), and N₂-cyclopropylguanine (^CPG). Both biochemical reaction with a variety of photooxidants and electrochemistry show that the modified bases, ^CPC and ^CPG, have similar redox properties as the natural DNA bases and are irreversible kinetic traps by ring opening on the picosecond time scale.

In DNA assemblies containing either [Rh(phi)₂(bpy')]³⁺ (Rh) or an anthraquinone derivative (AQ), two high energy photooxidants, appreciable oxidative damage at a distant ^CPC is observed, which shows that hole migration must involve also the higher energy pyrimidine bases. The damage yield is modulated by lower energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at ^CPC is similar to that at flanking ^CPG. Thus, HT is not simply a function of the relative energies of the isolated bases, but instead may require orbital mixing among the bases. Hole migration through DNA involves occupation of all the DNA bases with radical delocalization.

The oxidation of ^CPC via distant photooxidants has been found also to be sensitive to intervening structure and sequences. AQ-modified DNA assemblies of identical base composition but different base sequence have been probed. Single and double base substitutions within A-tracts modulate ^CPC decomposition. In fact, the entire sequence within the DNA assembly is seen to govern ^CPC oxidation, not simply the bases intervening between ^CPC and the tethered photooxidant.

These data are reconciled in a mechanistic model of conformationally gated hole transport through delocalized DNA domains. Oxidation of ^CPG separated from a tethered photooxidant by A-tracts with a series of lengths over 50 A exhibits a nonmonotonically periodic distance dependence and shows that the domain sizes in the A-tract is 4-5 base pairs. Sequence-dependent DNA structure and dynamics are essential to the transient formation of the domains and hole propagation among the domains. This dynamic, delocalized model provides a basis to reconcile and exploit DNA HT chemistry.

Just as long-range hole transport through DNA has now been established, DNA-mediated electron transport has not been as well characterized. Three iridium complexes have therefore been designed in order to initiate both photooxidative and photoreductive reaction of DNA and allow direct comparison between the two. Redox potentials of excited Ir complexes are determined by both triplet energy (E0-0) and ground state redox potentials. Two of the iridium complexes prepared have excited state potentials that are suffcient to oxidize purines, but not pyrimidines. The excited state oxidation potentials of three Ir complexes are around -1.0 V and would be able to reduce DNA pyrimidines. Both ^CPC and ^CPG in DNA can be decomposed by photoirradiation with the noncovalently bound iridium complexes. In particular, two of the complexes have the potential to probe oxidation of purines and reduction of pyrimidines in DNA.

Studies were also conducted using one of the iridium complexes covalently tethered to DNA oligonucleotides. Hence the metal complex serves as both a photooxidant and photoreductant in the study of DNA-mediated hole and electron transport. In the Ir-tethered DNA assemblies, a metal complex stabilizes the DNA duplex through its intercalative, functionalized dppz ligand. Cyclopropylamine-substituted bases, ^CPC and ^CPG, are used as kinetic fast electron and hole traps to probe the resulting charge migration processes after direct photoirradiation of the assemblies. Reductive decomposition of ^CPC via ET as well as the oxidation of ^CPG via HT is observed. Thus, the iridium tethered DNA containing cyclopropylamine-substituted bases provides a unique model system to explore the two DNA-mediated charge transport processes through the same DNA bridges. For the first time, ET and HT can be initialized by the same photoredox probe employing the identical electronic interaction mode with DNA.

A flash quench technique was also applied to Iridium-tethered DNA in order to generate the ground state photoreductant and initiate photoreduction using 5'-bromo-uridine (^BrU) as the electron trap. Efficiencies of ^BrU reduction in Ir-DNA upon flash quench technique was found to be comparable to that of ^CPG oxidation upon direct photoirradiation of Ir-DNA. Furthermore, in Ir-tethered DNA assemblies containing ^CPG or ^BrU as either the hole or electron trap, the sequence dependence of HT versus ET through an A-tract was examed. When ^CPG and ^BrU are placed in either purine or pyrimidine strands in A-tract, decomposition of both modified bases are observed. Thus, transient electron occupancy during ET, as well as hole occupancy during HT, are distributed onto both purine and pymidine strands in A-tract. Additionally, ^BrU decomposes in a more efficient fashion when it is located on a thyime-containing strands, which indicates that DNA-mediated ET prefers to pyrimidine strands rather than purine strands.

Thesis Files