Catalytic reduction of NAD(P)⁺ to NAD(P)H

1,4-Dihydronicotinamide adenine dinucleotide (NADH) and its phosphate ester (NADPH) are essential cofactors required for all living cells, playing pivotal roles in multiple biological processes such as energy metabolism and biosynthesis. NADPH is produced during photosynthesis by the combination of photosystem II, where water is oxidised, and photosystem I, where NADP⁺ is reduced. This review focuses on catalytic NAD(P)⁺ (and its analogues) reduction to generate 1,4-NAD(P)H without formation of other regioisomers and the dimer. There are different ways for production of 1,4-NAD(P)H and its analogues. Firstly, electrocatalytic reduction of NAD(P)⁺ is discussed to clarify how the regioselective reduction of NAD(P)⁺ to 1,4-NAD(P)H is achieved with use of metal complex catalysts. The applied potential for the electrocatalytic reduction of NAD(P)⁺ to 1,4-NAD(P)H is much reduced by combination with the photocathode under photoirradiation. Then, mechanisms of hydrogenation of NAD(P)⁺ by H₂ and transfer hydrogenation of NAD(P)⁺ by formate used as an electron and proton source to produce 1,4-NAD(P)H are discussed. Hydroquinone derivatives are also used as plastoquinol analogues, which act as hydride sources in a photosystem I model reaction, in which NAD(P)⁺ and its analogues are reduced by hydroquinone derivatives to form 1,4-NAD(P)H and its analogues using an NAD(P)⁺ reduction catalyst and a photoredox catalyst. The photosystem I model is then combined with a photosystem II model in which plastoquinone analogues are reduced to plastoquinol analogues by water to achieve the stoichiometry of photosynthesis, that is, photocatalytic reduction of NAD(P)⁺ by water.