Electroenzymatic Aromatic Nitration via an Electric Field and Electro-Mediator

Electrochemistry enables numerous redox enzymatic reactions with high efficiency. Nitroaromatic molecules with diverse biological properties have been extensively applied in medicine. New strategies are continuously required for the nitration of aromatic molecules with improved yields and selectivity. Here, we report a reaction by combining electrochemistry and the enzyme ferredoxin-TxtE to drive the nitration of l-tryptophan (l-Trp). With methyl viologen as the electron mediator, such an electroenzymatic approach avoids the use of expensive β-nicotinamide adenine dinucleotide phosphate (NADPH) and results in a higher yield than the wild-type ferredoxin-NADP+ reductase-TxtE reaction. This electrochemically driven reaction also produces two nitro-l-Trp isomers, i.e., 4-nitro-l-Trp and 5-nitro-l-Trp, which can be regulated by an electric field and electron mediators. Moreover, when more polarized mediators are used, the selectivity is recovered to 4-nitro-l-Trp. The mechanistic study suggests that the selectivity of the electron mediators is attributed to the steric hindrance and polarity of bipyridiniums. This work affords a new catalytic strategy for the regulation and control of electroenzymatic catalysis, which is expected to extend the application of electroenzymatic reactions in synthesis, energy, and sensing fields.