Regioselective Reduction of NAD⁺ to 1,4‐NADH with a Bioinspired Metal Sulfide Electrocatalyst

Abstract

Nicotinamide adenine dinucleotide (NAD(P)H) is an important energy carrier and charge transfer mediator in organisms. The efficient and regioselective reduction of NAD(P) + to NAD(P)H is of significance in biocatalysis, nature and artificial photosynthesis, but remains challenging with artificial heterogeneous catalysts. Inspired by nature oxidoreductases where active centers are transition metal sulfide clusters, here we report that CoMo 2.75 S x is efficient for the regiospecific electrocatalytic reduction of NAD + to NADH, achieving a selectivity as high as 89 % for 1,4-NADH. It is found that the adsorbed hydrogen and hydride formed on electrode surface are crucial for the selective formation of 1,4-NADH. Based on isotopic effect, the CÀ H bond formation process by hydride transfer to NAD + is inferred to be the rate-determining step for NADH formation, which mimics enzyme catalyzed NADP + reduction process in nature photosynthesis.

Synergy Between Metal and Molecular Catalysts for (Photo)electrocatalytic 1,4-NADH Regeneration

“…We tried to reveal the essence of the synergy between Cu and molecular catalyst for the NAD + reduction reaction. On the basis of our previous researches on direct NAD + reduction with metals and metal sulfides, there may be some hydrogen species on the Cu surface under cathodic potential that may participate in the NAD + reduction process. , Therefore, we used the electron paramagnetic resonance (EPR) technique to detect the hydrogen species on Cu and carbon electrodes in the presence and absence of M in the electrolyte. H ad atoms may diffuse into the nearby electrolyte and form H • radicals, which can be captured by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO).…”

“…29,30 Moreover, previous works have shown that hydrogen species play crucial roles during electrocatalytic NAD + reduction reaction. 31,32 Hence, we are motivated to couple metals and molecular catalysts for (photo)electrocatalytic NAD + reduction reactions to find a way for efficient 1,4-NADH regeneration.…”

“…Metallic and metal sulfide catalysts have been proven to be active for direct mediator-free (photo)­electrocatalytic NAD + reduction reactions, ,− but the reduction site of NAD + is uncontrollable, leading to low selectivity for 1,4-NADH formation with large amounts of side products, 1,6-NADH and NAD 2 . Noble metal complexes, especially [Cp*Rh­(bpy)­(H 2 O)]­Cl 2 (abbreviated as M , bpy = 2,2′-bipyridine, Cp* = pentamethylcyclopentadienyl), show high selectivity for 1,4-NADH production. , However, its activity is low because the formation of metal-hydride ( M-H ) active species via electron and proton transfer is sluggish. , We noted that transition metal catalysts are widely used for electrocatalytic hydrogen evolution or hydrogenation reaction involving active hydrogen species. , Moreover, previous works have shown that hydrogen species play crucial roles during electrocatalytic NAD + reduction reaction. , Hence, we are motivated to couple metals and molecular catalysts for (photo)­electrocatalytic NAD + reduction reactions to find a way for efficient 1,4-NADH regeneration.…”

A Coupled System of Ni3S2 and Rh Complex with Biomimetic Function for Electrocatalytic 1,4-NAD(P)H Regeneration

“…In nature, metal sulfide clusters can act as charge-transfer mediators or active centers of enzymes for (de)hydrogenation reactions. , During the reduction of NADP + by FNR, the ferredoxin (Fd) cofactor with a [Fe 2 S 2 ] redox center functions as an electron-transfer mediator to reduce flavin adenine dinucleotide (FAD) to FADH – , which can convert NADP + to 1,4-NADPH . We recently developed a bioinspired CoMo 2.75 S x catalyst for direct electrocatalytic NAD + reduction through a hydride (H – )-transfer mechanism and achieved a high selectivity of 89% in 1,4-NADH . Besides, MoS x displayed similar performance to CoMo 2.75 S x .…”

Bioinspired photoelectrochemical NADH regeneration based on a molecular catalyst-modified photocathode

“…10 PEC NADH regeneration has been reported for heterogeneous catalyst-modified p-type semiconductor photocathodes, such as Pt/ p-GaAs and CoMo 2.75 S x /p-Si. 11,12 However, biologically inactive side products such as 1,6-NADH and NAD 2 have been found in these heterogeneous catalyst-based PEC systems. Molecular organometallic catalysts containing ruthenium, rhodium, and iridium have been developed for highly selective electrochemical NADH regeneration.…”