DNA-Accelerated Copper Catalysis of Friedel–Crafts Conjugate Addition/Enantioselective Protonation Reactions in Water

Abstract

DNA-induced rate acceleration has been identified as one of the key elements for the success of the DNA-based catalysis concept. Here we report on a novel DNA-based catalytic Friedel-Crafts conjugate addition/enantioselective protonation reaction in water, which represents the first example of a reaction that critically depends on the >700- to 990-fold rate acceleration caused by the presence of a DNA scaffold. The DNA-induced rate acceleration observed is the highest reported due to the environment presented by a biomolecular scaffold for any hybrid catalyst, to date. Based on a combination of kinetics and binding studies, it is proposed that the rate acceleration is in part due to the DNA acting as a pseudophase, analogous to micelles, in which all reaction components are concentrated, resulting in a high effective molarity. The involvement of additional second coordination sphere interactions is suggested by the enantioselectivity of the product. The results presented here show convincingly that the DNA-based catalysis concept, thanks to the DNA-accelerating effect, can be an effective approach to achieving a chemically challenging reaction in water.

Fluorescence Spectroscopic Insight into the Supramolecular Interactions in DNA‐Based Enantioselective Sulfoxidation

“…It should be noted that the thioanisole substrate also shows a binding interaction with HT21 (Figures H and ). A similar phenomenon between substrates and metal cofactor/dsDNA hybrid catalysts was also found by Roelfes et al . It was proposed that these interactions of substrate and cofactor with dsDNA increased the effective molarity of substrate and cofactor, which resulted in rate acceleration.…”

“…In 2016, Roelfes et al. reported that the rate of Cu II –bipyridine catalyzing the Friedel–Crafts addition/enantioselective protonation reaction could be increased by as much as 990‐fold due to the presence of double‐stranded (ds) DNA . Spectral experiments suggested that Cu II –bipyridine interacted with dsDNA through groove binding The groove of dsDNA acted as a pseudophase to concentrate substrates, which resulted in the activity enhancement of the copper cofactor …”

Rational design of metalloenzymes: From single to multiple active sites

“…A very recent study by Roelfes and co-workers [182] showed that upon binding of Cu(II) complexes, such as Cu(II)(dmbipy)(NO3)2 complex, to a DNA scaffold, the Friedel-Crafts reaction was enhanced >700-to 990-fold. DNA-accelerating effect was also observed for other reactions such as carbene-transfer reactions catalyzed by cationic iron-porphyrin [183], which suggests that DNA scaffolds are alternative to protein scaffolds, with potential applications in design of functional metalloenzymes.…”

Dynamics of Metal Complex Binding in Relation to Catalytic Activity and Selectivity of an Artificial Metalloenzyme

“…21 These two reactions share similiraties, but the chiral center is created in different elementary reaction steps. 22 The conjugate addition of 5-methoxy-1H-indole (2b) to 2-methyl-1-(thiazol-2-yl)prop-2-en-1-one (4) was used as benchmark FC/EP reaction (Fig. 1d).…”