Pnictogen-Bonding Enzymes

Angew Chem Int Ed Engl. 2024 Nov 4;63(45):e202411347. doi: 10.1002/anie.202411347. Epub 2024 Sep 5.

Abstract

The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a σ-hole interaction that is essentially absent in biocatalysis. For this purpose, stibine catalysts were equipped with a biotin derivative and combined with streptavidin mutants to identify an efficient transfer hydrogenation catalyst for the reduction of a fluorogenic quinoline substrate. Increased catalytic activity from wild-type streptavidin to the best mutants coincides with the depth of the σ hole on the Sb(V) center, and the emergence of saturation kinetic behavior. Michaelis-Menten analysis reveals transition-state recognition in the low micromolar range, more than three orders of magnitude stronger than the millimolar substrate recognition. Carboxylates preferred by the best mutants contribute to transition-state recognition by hydrogen-bonded ion pairing and anion-π interactions with the emerging pyridinium product. The emergence of challenging stereoselectivity in aqueous systems further emphasizes compatibility of pnictogen bonding with higher order systems catalysis.

Keywords: Artificial enzymes; catalysis; pnictogen bonds; transfer hydrogenation.

MeSH terms

  • Biocatalysis
  • Biotin / chemistry
  • Biotin / metabolism
  • Hydrogen Bonding
  • Hydrogenation
  • Kinetics
  • Molecular Structure
  • Quinolines* / chemistry
  • Quinolines* / metabolism
  • Streptavidin / chemistry
  • Streptavidin / metabolism

Substances

  • Quinolines
  • Streptavidin
  • Biotin