Biocatalytic C=C Bond Reduction through Carbon Nanodot‐Sensitized Regeneration of NADH Analogues

Abstract

Light-driven activation of redox enzymes is an emerging route for sustainable chemical synthesis. Among redox enzymes, the family of Old Yellow Enzyme (OYE) dependent on the nicotinamide adenine dinucleotide cofactor (NADH) catalyzes the stereoselective reduction of α,β-unsaturated hydrocarbons. Here, we report OYE-catalyzed asymmetric hydrogenation through light-driven regeneration of NADH and its analogues (mNADHs) by N-doped carbon nanodots (N-CDs), a zero-dimensional photocatalyst. Our spectroscopic and photoelectrochemical analyses verified the transfer of photo-induced electrons from N-CDs to an organometallic electron mediator (M) for highly regioselective regeneration of cofactors. Light triggered the reduction of NAD and mNAD s with the cooperation of N-CDs and M, and the reduction behaviors of cofactors were dependent on their own reduction peak potentials. The regenerated cofactors subsequently delivered hydrides to OYE for stereoselective conversions of a broad range of substrates with excellent biocatalytic efficiencies.

Flavoenzyme‐mediated Regioselective Aromatic Hydroxylation with Coenzyme Biomimetics

“…So far, NCBs have been applied in stoichiometric amounts to biocatalytic reactions. An efficient recycling system, whether chemically with transition metals, [39] or enzymatically with a dehydrogenase enzyme, [9c,30,40] is still limited by turnover numbers lower than a few hundred, but will hopefully be overcome by new computational modeling and protein engineering approaches in the near future. [40] Additionally, as differently substituted NCBs can lead to variable stability and redox potential as well as enzyme specificity, the type of NCB should match the enzyme desired to catalyze a reaction.…”

Biocatalysis Fueled by Light: On the Versatile Combination of Photocatalysis and Enzymes

“…Although excellent yields and enantioselectivities were achieved for the product 42 h , with cinnamaldehyde ( 41 c ) as a substrate the yield was only moderate. Further variants of this transformation included the use of nitrogen‐doped CDs as photosensitizer coupled with the nicotinamide mimic mNADs 12 c – 12 e or [CpRh(bpy)H 2 O] 2+ ( 22 ) as mediators …”

“…[ a] Reactionmixtures werei rradiatedu nder inert atmosphere with visible light (l > 420 nm; [ b] in the presence of MV 2 + (23); [c] control with use of stoichiometric amounts of NADH. [36] [42] TOYE/ PETNR [a] 42 b -> 99/89 [42] TOYE/ PETNR [a] 42 c -80/85 [42] TOYE/ PETNR [a] 42 d 9/376 8/22 [42] TOYE/ PETNR [a] 42 e 6/857 3/65 [42] TOYE/ PETNR [a] 42 f > 99/ > 99 82/10 [42] TOYE/ PETNR [a] 42 g 98/ > 99 6/5 [42] 16 a -TEA Ts OYE/YqjM 42 h > 99 76/84 [43] Ts OYE/YqjM 42 c -34/32 [43] N-CD 22 TEA Ts OYE 42 h 93 86 [44]…”

“…Further variants of this transformation included the use of nitrogen-dopedC Ds as photosensitizer coupled with the nicotinamide mimic mNADs 12 c-12 e or [CpRh(bpy)H 2 O] 2 + (22)a sm ediators. [44]…”

Nature is the Cure: Engineering Natural Redox Cofactors for Biomimetic and Bioinspired Catalysis

“…Furthering their work on the photoregeneration of enzymes from the Old Yellow Enzymes (OYEs) family, Paul, Hollmann and Park have reported the regeneration of synthetic NADH analogues through the use of N‐doped carbon nanodots (N−CDs) . In this example, the overall NADH/FMN manifold is preserved but the NADH cofactor is replaced by a synthetic analogue.…”