Silver(I)‐Boosting Cytidine Triphosphate‐Based Enantioselective Catalysis

ABSTRACT Due to their natural abundance, multiple binding sites, and biocompatibility, nucleotides are emerging as versatile scaffolds to construct biohybrid catalysts. The nucleotide‐metal complexes have been proven to exhibit enantioselective catalytic activity, yet achieving chiral tunability and understanding the origin of enantioselectivity remain challenging. Herein, we found that Ag + ions could induce the enantioselective catalytic activity of cytidine triphosphate/dipyridophenazine‐copper(II) nitrates (CTP/Cu(dppz)(NO 3 ) 2 ) in Diels‐Alder reactions upon the formation of cytosine‐silver(I)‐cytosine (C‐Ag + ‐C) base pairs. The CTP(Ag + )/Cu(dppz)(NO 3 ) 2 ‐catalyzed Diels‐Alder reaction of azachalcone and cyclopentadiene gives rise to 96% conversion and 65% enantiomeric excess, while CTP/Cu(dppz)(NO 3 ) 2 exhibits almost no catalytic activity. Based on ultraviolet–visible (UV‐Vis) spectroscopy, circular dichroism (CD) spectroscopy, electron paramagnetic resonance (EPR), Fourier transform infrared (FT‐IR) spectroscopy, Raman spectroscopy, x‐ray photoelectron spectroscopy (XPS) and nuclear magnetic resonance (NMR), we demonstrate that Ag + ion promotes the formation of CTP‐Ag + ‐CTP serving as a chiral auxiliary and reveal the plausible supramolecular structure of CTP(Ag + )/Cu(dppz)(NO 3 ) 2 assembly through electrostatic and π–π stacking interactions. Moreover, the successful heterogenization of this system into coordination polymers retains high activity and silver‐enhanced enantioselectivity, resulting in a practical solid catalyst. This work establishes the metal‐mediated base pairing as a powerful design principle for biohybrid catalysts and opens a pathway to efficient heterogeneous catalytic systems.