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Chemische Photokatalyse mit Oligonucleotiden und kurzen Peptiden

Fachliche Zuordnung Biologische und Biomimetische Chemie
Förderung Förderung von 2014 bis 2022
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 255037740
 
Erstellungsjahr 2022

Zusammenfassung der Projektergebnisse

Light has ambivalent properties: On the one side, light is dangerous, and exposure of DNA to solar light, in particular energy-rich UV light, is as frequent and serious threat for the integrity of the genetic information by photodamages. On the other side, light is a sustainable energy source for chemical transformations. Classic photosensitization and modern photoredox catalysis are combined under the roof of “chemical photocatalysis”. We studied this ambivalence of light in two project parts A and B. Project part A. Exposure of DNA to solar light, in particular energy-rich UV light, is a serious threat for the integrity of the genetic information by photodamages. In contrast to the established mechanisms to photodamages, the possibility to observe such damages far, meaning more than 5 base pairs away from the site of photoexcitation has only partially explored and understood. The exact definition of the site of photoexcitation as energy donor and the site of energy acceptor is an important prerequisite for the experimental study of this phenomenon. We followed this principle and constructed a new type of DNA architecture that allowed us to determine the distance dependence of energy transport through DNA directly by the formation of remote photodamages. We used benzophenones, acetophenone and xanthones as photosensitizers and placed them as artificial nucleosides into DNA, together with a designated single site of DNA photodamaging. With the benzophenone and acetophenone photosensitizers we observed an exponential, but very shallow distance dependency for the DNA photodamaging, consistent with triplet energy transport, but as a step-by-step hopping process over the base pairs. In contrast, with xanthone as photosensitizer we observed a sigmoidal distance dependence. Remote photodamages were observed over distances of up to 105 Å (30 A-T pairs) which could only be explained by a singlet energy hopping process that might work more efficiently than the triplet energy hopping induced by the benzophenones. The final distance limit for such remote CPD formation may still not be discovered, since the current limit of 105 Å was set by the experiment. We developed also a photoDNAzyme to gain enantioselectivity for the photosensitized intramolecular [2+2]-cycloaddition of a quinolinone substrate in aqueous solution. This is the first reported chirality transfer from DNA to a photochemical reaction. Project part B. For the photoredox catalytic nucleophilic addition of alcohols to styrene derivatives, we could show that the regioselectivity can be controlled by the type of photoinduced charge transfer that was initiated by the photoexcited catalyst. One of the major drawbacks of these photocatalytic conversions was the use of additives as electron shuttles to promote the efficiency of forward and backward electron transfers. In order to avoid these additives, we designed short peptides with binding sites that fix the substrates for the electron transfer process during the whole photocatalytic cycle. Thereby, we established the concept of “photozymes”, small peptides with a proline-type turn show photocatalytic activity without the need for additives. Furthermore, we developed alkylaminosubstituted phenothiazines as strongly reducing photocatalysts, able to convert even alkyl olefins. The photoredox catalytic reactions require remarkably low catalyst loadings and yield the alkoxylation products in high yields. Although substrate binding is probably unspecific, the concept of “photozymes” for photoredox catalysis has significant potential for other photocatalytic reactions, in particular with respect to enantioselective photocatalysis. Surprises: Project part A. The sigmoidal distance dependence of remote photodamaging for the DNA architectures with xanthones: The distance limit for remote photodamaging is still not determined, as our longest distance of 105 Å was set by the photostability of the applied fluorescent marker (Atto dye). Project part B. The unconventional photoredox catalytic cycle observed for the peptide as “photozyme” modified with the dicyano perylene bisimide: The catalytic cycle operates via the radical anion and the dianion of the photoredox catalyst as intermediates. “DN-Schäden durch wandernde Lichtenergie. UV-Strahlung verändert DNA auch sehr weit entfernt von der Eintrittsstelle des Lichts“ https://www.kit.edu/kit/pi_2020_074_dna-schaden-durch-wandernde-lichtenergie.php

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