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978-3-8439-0240-3, Reihe Organische Chemie
Synthesis and evaluation of redox-center modified DNA
155 Seiten, Dissertation Ludwig-Maximilians-Universität München (2011), Softcover, A5
Excess electron transfer processes in DNA were investigated as they are associated with the repair of UV lesions. Indeed DNA-photolyase repair enzymes use a light-excited, reduced and deprotonated flavin as an electron donor to achieve the repair of some of these lesions through a single electron injection into the lesions. The capture of the electron by the lesion is followed by a fragmentation reaction that leads to repaired DNA. We developed a new DNA system consisted of three strands: a leader strand containing a flavin unit as electron donor and two single strands containing the electron acceptors. This model system allowed to calculate overall maximum rates for cleavage of CPD dimer. The same flavin unit was used in DNA hairpins as electron acceptor. FAD and FMN cofactors, in the oxidized state, are known to photooxidize the bases in duplex DNA, which leads to severe oxidative DNA damage. The fact that UV-A or visible light causes mutations even though DNA does not absorb in this wavelength region is thought to be the result of such flavin-cofactor-mediated DNA photooxidation processes.
It was demonstrated that electron transfer process in the series H1-H4 is governed by a direct superexchange-based mechanism. In the hairpin series H5 H7, however, the electron donation is dominated by a hopping mechanism. Indeed they showed identical S1 decay timescales probably due to the hopping of the electron through the dA:dT sequence which represents the rate determining step. In the latter series the formation of long-lived charge separated state was observed. The quantum yields of the charge separated state resulted varied with the number of stacking dG bases, being the highest for H7. In Chapter 4 the possibility to form a metal-salen complex along the major groove of DNA was investigated. Alkyne-modified DNA was constructed using modified uridine nucleosides via their corresponding phosphoramidites. The post-synthetic functionalization of the DNA via “click chemistry” allowed the introduction of the salicylic aldehyde in the desired position. The newly formed strands were treated with ethylenediamine to form the salen ligand and subsequently the metal ions were added to form the complex. The coordination of several metal ions was studied. The complexes were fully characterized by ESI measurements and UV-Vis titrations.