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On the distance-independent hole transfer over long (A-T),,-sequences in DNA

Furrer, Ernst. On the distance-independent hole transfer over long (A-T),,-sequences in DNA. 2004, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_6927

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Abstract

For the purposes of site-selective charge injection into guanine-free DNA, a new synthetic route towards a 4'-pivaloylated adenosine derivative was developped, enabling the study of long-range charge transfer in DNA. The synthesis of 4'-pivaloylated adenosine 46 succeeded in 0.5% yield over 10 steps, providing a DNA-synthesizer compatible building block. Photolysis of single- or double-stranded 29mer 103 demonstrated that the generated ribose radical cation is most efficiently reduced by electron transfer from adenine at pH 5.0 in 20 % absolute yield. This process yields an adenine radical cation and thus promotes a positive charge into the DNA base stack. Experiments with DNAs containing long guanine-free sequences have shown that, once the positive charge is injected into an (A−T)n sequence, a rapid and distance-independent charge transfer mechanism involving adenines as charge carriers is established. A guanine-hopping mechanism[27,151] was excluded due to lack of guanines in these DNAs. Instead, a partial thermodynamic charge distribution was observed. The apparently highly-efficient charge transport over long (A−T)n sequences was shown to be easily disrupted by structural changes in the base-pairing. This was studied by introduction of a series of base mismatches and an abasic site opposite an adenine. Higher solvent accessibility of the damaged sites accounted for deprotonation and thus charge loss from the acidic adenine radical cation. Protonation of adenine inside an A−C wobble base pair also decreased the charge transfer efficiency. The abnormal structural changes found in A-tracts of duplex DNA were shown to increase the charge transfer efficiency over long (A−T)n sequences as they imply an improved DNA duplex structure providing a higher stacking area and shorter base-base distances. This work has shown that, although the field of charge transfer over long (A−T)n sequences is new and little understood, the charge transport mechanism is thought to be a rapid, multistep process involving adenines as charge carrier where the charge may hop from adenine to adenine or may be delocalized in polaron-like species.
Advisors:Giese, Bernd
Committee Members:Woggon, Wolf-Dietrich
Faculties and Departments:05 Faculty of Science > Departement Chemie > Former Organization Units Chemistry > Bioorganische Chemie (Giese)
UniBasel Contributors:Giese, Bernd and Woggon, Wolf-Dietrich
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:6927
Thesis status:Complete
Number of Pages:134
Language:English
Identification Number:
edoc DOI:
Last Modified:05 Apr 2018 17:31
Deposited On:13 Feb 2009 15:10

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