Fundamental aspects of DNA-mediated charge transport

back electron transfer;bridge energetics;DNA charge transport;ionic distribution;photooxidants;sequence composition

Williams, Tashica Treshun ; Barton, Jacqueline K.

University:California Institute of Technology

Department:Chemistry and Chemical Engineering

关键词: back electron transfer;    bridge energetics;    DNA charge transport;    ionic distribution;    photooxidants;    sequence composition;   

Others  :  https://thesis.library.caltech.edu/1305/1/thesis.pdf

美国|英语

来源: Caltech THESIS

【 摘 要 】

The pi-stacked array of DNA base pairs has fascinated scientists since its structural delineation.Here are described fundamental studies to probe how this pi-stacked array mediates DNA charge transport (CT).Intercalators, such as dipyridophenazine (dppz) complexes of ruthenium and phenanthrenequinone diimine (phi) complexes of rhodium, serve as powerful and systematic probes of DNA CT in these studies.In a series of rhodium-tethered DNA assemblies, with varying A/T sequences intervening between guanine doublet sites (5?-GG-3?), long-range oxidative DNA damage is examined.The guanine doublet sites are known as sites of low oxidation potential in DNA, and the rhodium complex serves as a spatially separated, potent photooxidant.Although these studies are inconsistent with a mechanism involving guanine hopping and tunneling through A/T sequences, these data illustrate that the sequence of bases is an important determinant in attenuating oxidative damage yields of CT.Based on these data, we propose hopping among domains defined by sequence-dependent structure.Additional studies are also described using rhodium-tethered DNA assemblies to examine how different ionic distributions around the DNA duplex modulate DNA CT.In the rhodium-DNA conjugates, differences in long-range oxidative damage yield were observed depending on the position of pendent charges on the oligomer.A direct comparison of DNA CT utilizing a variety of oxidants has also been performed.CT is assayed both through determination of the yield of oxidative guanine damage and, in derivative DNA assemblies, by analysis of the yield of a faster oxidative trapping reaction, ring-opening of N2-cyclopropylguanine (CPG) within the DNA duplex.We find clear differences in oxidative damage ratios at the distal versus proximal 5?-CGGC-3? depending upon the photooxidant employed.There is also a correlation seen between absolute yield of oxidative damage and distal/proximal damage ratio; photooxidants that produce higher distal/proximal damage ratios have lower yields.These differences observed among photooxidants as well as the complex distance dependence are attributed to differences in rates of back electron transfer (BET).A study of the overall effect of bridge energetics on DNA CT has also been performed by constructing rhodium-DNA assemblies containing varying numbers of inosine, a guanine base analog with a higher oxidation potential, between two 5?-GG-3? sites.For the rhodium conjugates, only a slight diminution in distal oxidative yield with increasing distance is observed, suggesting direct charge injection by rhodium into higher energy sites of the intervening bridge.These results, taken together, provide insight into salient parameters that govern DNA CT, in particular how energetics, charge distribution, and sequence-dependent DNA structure and dynamics modulate charge migration through DNA.