Chemical photocatalysis with oligonucleotides and short peptides
Final Report Abstract
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
Publications
- Photocatalytic nucleophilic addition of alcohols to styrenes in Markovnikov and anti- Markovnikov orientation. Beilstein J. Org. Chem. 2015, 11, 568-575
M. Weiser, S. Hermann, A. Penner, H.-A. Wagenknecht
(See online at https://doi.org/10.3762/bjoc.11.62) - Synthesis of benzophenone nucleosides and their photocatalytic evaluation for [2+2]- cycloaddition in aqueous media. Eur. J. Org. Chem. 2015, 6661-6668
N. Gaß, H.-A. Wagenknec
(See online at https://doi.org/10.1002/ejoc.201500885) - Elucidation of the Dexter-type energy transfer in DNA by thymine-thymine dimer formation using photosensitizers as artificial nucleosides. Angew. Chem. Int. Ed. 2017, 56, 1385-1389
L. Antusch, N. Gaß, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/anie.201610065) - Photocatalysis of a [2+2]-cycloaddition in aqueous solution using DNA three-way junctions as chiral photoDNAzymes. ChemPhotoChem 2017, 1, 48-50
N. Gaß, J. Gebhard, H.-A. Wagenknech
(See online at https://doi.org/10.1002/cptc.201600034) - Synthesis of N,N-dimethylpyrene-modified short peptides for chemical photocatalysis. J. Pept. Sci. 2017, 23, 563-566
S. Hermann, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/psc.2966) - Proline-rich short peptides with photocatalytic activity for the nucleophilic addition of methanol to phenylethylenes. Eur. J. Org. Chem. 2018, 2204-2207
S. Hermann, D. Sack, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/ejoc.201800319) - Significant fluorescence enhancement of N,N-dimethylaminobenzophenone after embedding as C-nucleoside in DNA. ChemPhotoChem 2018, 2, 12-17
C. Schweigert, N. Gaß, H.-A. Wagenknecht, A.-N. Unterreiner
(See online at https://doi.org/10.1002/cptc.201700183) - N-Arylphenothiazines as strong donors for photoredox catalysis - pushing the frontiers of nucleophilic addition of alcohols to alkenes. Beilstein J. Org. Chem. 2019, 15, 52–59
F. Speck, D. Rombach, H.-A. Wagenknecht
(See online at https://doi.org/10.3762/bjoc.15.5) - How Far Does Energy Migrate in DNA and Cause Damage? Evidence for Long- Range Photodamage to DNA. Angew. Chem. Int. Ed. 2020, 59, 17378- 17382
A. Kuhlmann, L. Bihr, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/anie.202009216) - N-Arylbenzo[b]phenothiazines as Reducing Photoredox Catalysts for Nucleophilic Additions of Alcohols to Styrenes: Shift towards Visible Light. Synlett 2021, 32, 582-586
F. Seyfert, H.-A. Wagenknecht
(See online at https://doi.org/10.1055/a-1304-4575) - Nucleophilic Alkoxylations of Unactivated Alkyl Olefins and alpha-Methyl Styrene by Photoredox Catalysts. Eur. J. Org. Chem. 2021, 773-776
F. Seyfert, M. Mitha, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/ejoc.202001533) - The Concept of Photozymes: Short Peptides with Photoredox Catalytic Activity for Nucleophilic Additions to α-Phenyl Styrenes. Eur. J. Org. Chem. 2021, 6400-6407
D. Sack, H.-A. Wagenknecht
(See online at https://doi.org/10.1002/ejoc.202101068) - Complementary photocatalytic toolbox: Control of intramolecular endo vs. exo-trig cyclizations of α-phenyl olefins to oxaheterocyclic products. Synlett 2022
F. Weick, D. Steuernagel, A. Belov, H.-A. Wagenknecht
(See online at https://doi.org/10.1055/s-0040-1719871) - Remote Photodamaging of DNA by Photoinduced Energy Transport. ChemBioChem 2022, 23, e202100265
H.-A. Wagenknecht
(See online at https://doi.org/10.1002/cbic.202100265)
