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Chemical photocatalysis with oligonucleotides and short peptides

寡核苷酸和短肽的化学光催化

基本信息

批准号：
255037740
负责人：
Professor Dr. Hans-Achim Wagenknecht
金额：
--
依托单位：
Institut für Organische Chemie (IOC)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/255037740?language=en
关键词：
Chemical photocatalysis oligonucleotides short peptides

项目摘要

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.

化学面临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，现在结合在“化学发光”的屋顶下。在该项目的第一个资助期，建议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，将进一步开发光催化活性DNA（项目部分A）和光催化亲核加成和寡肽（项目部分B），主要目标如下：项目部分A。通过双链DNA的三重态能量转移是限速步骤，如果三重态能量被动力学捕获，并通过T-T二聚体的产率随照射时间的推移进行分析。在该项目的第一个资助期内确定的T-T二聚体产率的指数距离依赖性最适合德克斯特型三重态-三重态能量转移机制，但对于从供体到T-T二聚化位点的连贯的一步过程来说太浅。因此，我们提出了一个逐步的三重态能量跳跃过程在长范围内（超过3-4个插入碱基对），由几个短程德克斯特型能量转移从单个碱基对，这是支持的理论。通过使用二苯甲酮和氧杂蒽酮作为DNA中的C-核苷，我们能够首次详细研究DNA损伤能量耗散的途径。充分理解通过DNA的三重态能量转移机制不仅对于光诱导DNA损伤的形成，而且对于在该项目的第一个资助期阐明的合成光DNA酶也是一项重要任务。项目B部分。对于光氧化还原催化亲核加成醇的苯乙烯衍生物，我们可以表明，区域选择性可以控制由光激发的催化剂引发的光诱导电荷转移的类型。苯乙烯底物的光还原产生Markovnikov型产物，而光氧化产生反Markovnikov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族和烷基化烯烃。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双酰亚胺来实现。双光子激发策略将进一步移动激发态电势。脯氨酸诱导的醛的烯胺将作为C-亲核试剂用于亲核加成，并且立体选择性通过基于脯氨酸的短肽实现。