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 = kappa(2)-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 mu mol 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. H-1 EXSY NMR unequivocally shows that a rapid equilibrium establishes between 1,6-NADH and 1,4-NADH (K-eq = 10.1, Delta G(0) = -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.