Uridine triphosphate hybrid catalyst for carbon‑carbon bond formation reactions with enhanced enantioselectivity by mercury(II) ions

Abstract

DNA hybrid catalysts are constructed by embedding active metal species into the chiral scaffolds of DNA, which have been successfully applied to some important aqueous-phase enantioselective transformations. Owing to simple components and inherent chirality, nucleotide hybrid catalysts are emerging in response to soving the unclear locations of catalytic centers and the plausible catalytic mechanisms in DNA-based asymmetric catalysis. However, the tertiary structure of nucleotides lacks tunability, severely impeding further design of nucleotide hybrid catalysts for potential applications. To this end, a design strategy for tunable nucleotide hybrid catalysts is put forward by introducing metal-mediated base pairs. Herein, we found that the formation of uracil‑mercury(II)-uracil (U-Hg²⁺-U) base pairs could enhance the enantioselectivity in uracil-containing nucleotide-based asymmetric reactions. Compared with uracil triphosphate (UTP) complexing with Cu²⁺ ions (UTP∙Cu²⁺), the presence of Hg²⁺ ions gave rise to an increased enantiomeric excess (ee) of 38 % in Diels-Alder reactions and 22 % ee in Michael reactions. The Hg²⁺-tuning behaviors of UTP hybrid catalyst have been demonstrated to largely depend on nucleotides, Hg²⁺ concentrations, metal cofactors, additives and reaction types. Based on ultraviolet-visible, circular dichroism and nuclear magnetic resonance spectroscopic techniques, the chiral enhancement of Hg²⁺-containing UTP hybrid catalyst is proved to largely depend on the formation of U-Hg²⁺-U base pairs and the plausible cross-linked structure of UTP-Hg²⁺-UTP/Cu²⁺ assembly. This work provides a tunable strategy based on the concept of metal-mediated base pairs, allowing further design of potent oligonucleotide-based catalysts for other enantioselective reactions.