Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride

Nat Chem. 2021 Apr;13(4):312-318. doi: 10.1038/s41557-020-00633-7. Epub 2021 Feb 18.

Abstract

Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcohols / chemical synthesis
  • Biocatalysis
  • Carbonic Anhydrase II / chemistry*
  • Carbonic Anhydrase II / metabolism
  • Humans
  • Hydrogen / chemistry*
  • Ketones / chemistry*
  • Ketones / metabolism
  • Models, Chemical
  • Molecular Docking Simulation
  • Oxidation-Reduction
  • Protein Binding
  • Silanes / chemistry*
  • Stereoisomerism
  • Zinc / chemistry*

Substances

  • Alcohols
  • Ketones
  • Silanes
  • Hydrogen
  • Carbonic Anhydrase II
  • CA2 protein, human
  • Zinc