Expanding biohybrid-mediated asymmetric catalysis into the realm of RNA

Abstract

The recent development of biohybrid catalytic systems has allowed synthetic chemists to reach high levels of selectivity on a wide variety of valuable synthetic transformations. In this context, DNA-based catalysts have emerged as particularly appealing tools. Interestingly, while long RNA sequences (ribozymes) are known to catalyse specific biochemical reactions with remarkable efficiencies, RNA-based catalysts involving a catalytically active metal complex interacting in a non-covalent fashion with short sequences have never been evaluated to date. We report here our results, which have led to the first example involving a short RNA-based catalyst.

Why DNA Is a More Effective Scaffold than RNA in Nucleic Acid‐Based Asymmetric Catalysis—Supramolecular Control of Cooperative Effects

“…The observations made in the catalysis experiments are in line with those by Smietana and Arseniyadis on hybrid catalysts for Friedel–Crafts alkylations formed from RNA oligonucleotides and copper complex 2 . Although they did not directly compare DNA‐ and RNA‐based catalysts, the enantioselectivity obtained with their RNA‐based catalysts was significantly reduced compared to corresponding DNA‐based catalysts described elsewhere .…”

“…Clearly, these results are only valid for copper complex 2 and its interaction with DNA/RNA to form a hybrid catalyst for Diels–Alder reactions. Smietana and Arseniyadis results indicate similar behavior of these type of hybrid catalysts in Friedel–Crafts alkylations . There is the possibility that another copper complex will show different behavior with RNA.…”

“…While DNA‐based hybrid catalysts have been intensively studied, RNA‐based hybrid catalysts were not reported. Only recently Smietana and Arseniyadis described investigations on a hybrid catalyst formed from copper complex 2 and double‐stranded RNA (dsRNA) . However, the hybrid catalysts obtained did not match the performance of comparable DNA‐based catalysts.…”

“…Only recently Smietana and Arseniyadis described investigations on ah ybrid catalyst formed from copperc omplex 2 and double-stranded RNA (dsRNA). [12] However,t he hybrid catalysts obtained did not matcht he performance of comparable DNA-based catalysts. With one specific RNA double-strand, moderate enantioinduction could be observed (up to 54 % ee), whereasmostother sequencesi nvestigated showed only low or no enantioinduction.…”

“…ee [d] [%] The observations made in the catalysis experiments are in line with those by Smietana and Arseniyadis on hybrid catalysts for Friedel-Crafts alkylations formed from RNA oligonucleotides and copper complex 2. [12] Although they did not directly compareD NA-and RNA-based catalysts, the enantioselectivity obtainedw ith their RNA-based catalysts was significantly reduced compared to corresponding DNA-based catalysts described elsewhere. [9c, g] There could be multiple explanations for the low enantioselectivities obtainedw ith RNA:f irst, the RNA could be degraded by the copper complex, which might act as at ype of artificial nuclease.…”