Chemical photocatalysis with oligonucleotides and short peptides

化学的主要挑战之一是加强利用光作为化学转化的可持续能源。经典的光敏化和现代的光氧化还原催化如今在“化学光催化”的框架下结合在一起。本项目第一资助期拟将寡核苷酸和寡肽应用于化学光催化。根据第一个资助期公布的结果，将根据以下主要目标进一步开发光催化活性DNA（项目A部分）和光催化亲核添加物和寡肽（项目B部分）：项目A部分：如果三重态能量被动力学捕获并通过照射时间内T-T二聚体的产率分析，则通过双链DNA的三重态能量转移是限速步骤。在本项目的第一个资助期，确定的T-T二聚体产率的指数距离依赖关系最适合dexter型三重态-三重态能量转移机制，但对于从供体到T-T二聚体位点的连贯一步过程来说太浅了。因此，我们提出了一种长距离（超过3-4个中间碱基对）的逐步三重态能量跳跃过程，该过程由几个短程的dexter型能量从单个碱基对转移到单个碱基对，这是有理论支持的。我们利用二苯甲酮和山酮作为DNA中的c核苷，首次详细研究了这种DNA损伤能量耗散的途径。充分了解DNA中三重态能量传递的机制不仅是光诱导DNA损伤形成的重要任务，也是本项目第一期资助期所阐明的合成photoDNAzymes的重要任务。对于醇到苯乙烯衍生物的光氧化还原催化亲核加成，我们可以证明区域选择性可以由光激发催化剂引发的光诱导电荷转移类型控制。苯乙烯底物的光还原产生马氏型产物，而光氧化产生反马氏型产物。本项目部分的中心目标是扩大这种光氧化还原催化反应性。底物范围将扩展到苯乙烯衍生物，并进一步扩展到非芳烃和烷基化烯烃。这需要增加激发态氧化还原电位，这将通过极富电子的n-苯基吩噻嗪和极贫电子的萘二亚胺来实现。双光子激发策略将进一步改变激发态势。脯氨酸诱导的醛类胺将作为亲核试剂用于亲核加成，立体选择性是由脯氨酸基短肽实现的。

One of the major challenges for chemistry is the enhanced use of light as sustainable energy source for chemical transformations. Classic photosensitization and modern photoredox catalysis are nowadays combined under the roof of "chemical photocatalysis". For the first funding period of this project it was proposed to apply oligonucleotides and oligopeptides for chemical photocatalysis. Based on the published results from the first funding period, both photocatalytically active DNA (project part A) and photocatalytic nucleophilic additions and oligopeptides (project part B) will be further developed with respect to following main objectives:Project part A. The triplet energy transfer through the double-stranded DNA is the rate-limiting step if the triplet energy is kinetically trapped and analyzed by the yield of T-T dimers over the irradiation time. The exponential distance dependence that was determined for the T-T dimer yield in the first funding period of this project fits best with a Dexter-type triplet-triplet energy transfer mechanism, but is too shallow for a coherent, one-step process from the donor to the site of T-T dimerization. Hence, we propose a stepwise triplet energy hopping process over long ranges (more than 3-4 intervening base pairs) that consists of several short-range Dexter-type energy transfers from single base pair to single base pair, which is supported by theory. By our approach using benzophenones and xanthones as C-nucleosides in DNA, we are able to study this pathway of DNA-damaging energy dissipation for the first time in detail. The full understanding of the mechanism of triplet energy transfer through the DNA is an important task not only for the formation of photoinduced DNA damages, but also for the synthetic photoDNAzymes that were elucidated in the first funding period of this project. 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. The photoreduction of styrene substrates yields the Markovnikov-type products, whereas the photooxidation yields the anti-Markovnikov-type products. The central objective of this project part is the broadening of this photoredox catalytic reactivity. The substrate scope will be extended to styrene derivatives and further to non-aromatic and alkylated olefins. This requires increased excited state redox potentials which will be achieved by extremely electron-rich N-phenyl phenothiazines and extremely electron-poor naphthalene bisimides. Two-photon excitation strategies will further shift the excited state potentials. Proline-induced enamines from aldehydes will be applied as C-nucleophiles for the nucleophilic additions, and stereoselectivity is achieved by proline-based short peptides.