Electrochemical NADH Regeneration Mediated by Pyridine Amidate Iridium Complexes Interconverting 1,4- and 1,6-NADH

Although there is a huge interest in redox mediators for the selective electrochemical regeneration of 1,4-NADH, only the class of rhodium compounds with bipyridine ligands, initially introduced by the pioneering work of Wienkamp and Steckhan (Wienkamp, R.; Steckhan, E. Angew. Chem. Int. Ed. Engl. 1982, 21, 782−783, 10.1002/anie.198207822), has been developed over the last few decades. Here we report the first two progenitors of a class of redox mediators for indirect NADH regeneration, namely [Cp*Ir(R′-pica)Cl] {pica = R′-picolinamidate = κ²-R′-pyridine-2-carboxamide ion (−1), 1 R′ = H and 2 R′ = Me}, which exhibit high TOF values (0.51 and 1.34 s^–1 for 1 and 2, respectively), a production rate of up to 3 μmol h^–1 cm^–2, and a faradaic efficiency of up to 99% for both complexes in 0.1 M phosphate buffer (pH 7, 298 K). The reaction exclusively leads to a mixture of 1,4-NADH, the desired product, and 1,6-NADH always in a 91:9 molar ratio, independently of the redox mediator, degree of conversion, and applied potential. ¹H EXSY NMR unequivocally shows that a rapid equilibrium establishes between 1,6-NADH and 1,4-NADH (K_eq = 10.1, ΔG⁰ = −1.4 kcal mol^–1, 298 K), in the presence of 1 and 2, suggesting that the latter are capable of rapidly interconverting the two regioisomers of NADH, thus allowing utilization of the totality of regenerated NADH.