Alkylations of simple electron-rich heterocompounds deliver valuable target structures in bioorganic and medicinal chemistry. Herein, we present a straightforward and photosensitizer free approach for the photoinduced CC coupling of electron-rich unsaturated heterocompounds with alkyl bromides using 405 nm and 365 nm irradiation. Comprehensive mechanistic studies indicate the involvement of 2,6-lutidine in the formation of a non-covalently bound intermediate to which the function of a photosensitizer is attributed. UV/Vis spectra reveal the formation of a bathochromic shifted band when the elec-[a

The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto-RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA-strand to give cytidine, which leads to an increase of pairing stability. If the proto-RNA contains a canonical seed-nucleoside with defined stereochemistry, the seed-nucleoside can control the configuration of the anomeric center that forms during the in-RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation.

5-Carboxycytosine (5caC) is a rare epigenetic modification found in nucleic acids of all domains of life. Despite its sparse genomic abundance, 5caC is presumed to play essential regulatory roles in transcription, maintenance and base-excision processes in DNA. In this work, we utilize nuclear magnetic resonance (NMR) spectroscopy to address the effects of 5caC incorporation into canonical DNA strands at multiple pH and temperature conditions. Our results demonstrate that 5caC has a pH-dependent global destabilizing and a base-pair mobility enhancing local impact on dsDNA, albeit without any detectable influence on the ground-state B-DNA structure. Measurement of hybridization thermodynamics and kinetics of 5caC-bearing DNA duplexes highlighted how acidic environment (pH 5.8 and 4.7) destabilizes the double-stranded structure by ∼10–20 kJ mol–1 at 37 °C when compared to the same sample at neutral pH. Protonation of 5caC results in a lower activation energy for the dissociation process and a higher barrier for annealing. Studies on conformational exchange on the microsecond time scale regime revealed a sharply localized base-pair motion involving exclusively the modified site and its immediate surroundings. By direct comparison with canonical and 5-formylcytosine (5fC)-edited strands, we were able to address the impact of the two most oxidized naturally occurring cytosine derivatives in the genome. These insights on 5caC’s subtle sensitivity to acidic pH contribute to the long-standing questions of its capacity as a substrate in base excision repair processes and its purpose as an independent, stable epigenetic mark.

The Front Cover shows the photosensitizer free, photoinduced C–C coupling of electron‐rich unsaturated heterocompounds with alkyl bromides using 405 nm and 365 nm irradiation. More information can be found in the Communication by O. Trapp et al.

Die Frage, wie sich die RNA als ein Träger der genetischen Information entwickelt hat, ist von grundlegender Bedeutung für unser Verständnis des Ursprungs des Lebens. Das RNA-Molekül ist viel zu komplex, als das es in einem einzigen Evolutionsschritt hat entstehen können, was darauf hindeutet, dass es Proto-RNAs (erste Vorläufer der RNA) gegeben haben könnte, die sich im Laufe der Zeit zu der heutigen RNA entwickelt haben. Hier zeigen wir, dass Isoxazol-Nukleoside, die aus Hydroxylamin, Cyanoacetylen, Harnstoff und Ribose gebildet werden, plausible Vorläufer für RNA sind. Das Isoxazol-Nukleosid kann sich innerhalb eines RNA-Strangs zu Cytidin umlagern, was zu einer Erhöhung der Paarungsstabilität führt. Wenn die Proto-RNA ein kanonisches seed-Nukleosid mit definierter Stereochemie enthält, kann das seed-Nukleosid die Konfiguration des anomeren Zentrums kontrollieren, das sich, während der in-RNA-Umwandlung bildet. Die Ergebnisse zeigen, dass sich die RNA nach der Strangbildung aus evolutionär primitiven Vorläufern wie Isoxazol-Ribosiden entwickelt haben könnte.