Hybrid Chemo-, Bio-, and Electrocatalysis for Atom-Efficient Deuteration of Cofactors in Heavy Water

Jack Rowbotham, Holly Reeve, Kylie Vincent

Research output: Contribution to journalArticlepeer-review


Deuterium-labeled nicotinamide cofactors such as [4-2H]-NADH can be used as mechanistic probes in biological redox processes and offer a route to the synthesis of selectively [2H] labeled chemicals via biocatalytic reductive deuteration. Atom-efficient routes to the formation and recycling of [4-2H]-NADH are therefore highly desirable but require careful design in order to alleviate the requirement for [2H]-labeled reducing agents. In this work, we explore a suite of electrode or hydrogen gas driven catalyst systems for the generation of [4-2H]-NADH and consider their use for driving reductive deuteration reactions. Catalysts are evaluated for their chemoselectivity, stereoselectivity, and isotopic selectivity, and it is shown that inclusion of an electronically coupled NAD+-reducing enzyme delivers considerable advantages over purely metal based systems, yielding exclusively [4S-2H]-NADH. We further demonstrate the applicability of these types of [4S-2H]-NADH recycling systems for driving reductive deuteration reactions, regardless of the facioselectivity of the coupled enzyme.

Original languageEnglish
Pages (from-to)2596-2604
Number of pages9
JournalACS Catalysis
Issue number5
Early online date11 Feb 2021
Publication statusPublished - 5 Mar 2021


  • Chemoenzymatic (Chemo-Bio)
  • Dihydrogen gas (H )
  • Electroenzymatic
  • H O (D O)
  • Heterogenous biocatalysis
  • Isotope labeling
  • Isotopic selectivity
  • Site-separated catalysis

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology


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