Reversible Electrocatalytic NAD<sup>+</sup>/NADH Interconversion Mediated by a Pyrazine-Amidate Iridium Complex
Gabriel Menendez Rodriguez, Caterina Trotta, Leonardo Tensi, Alceo Macchioni
Abstract
Herein, we report reversible electrocatalytic NAD + /NADH interconversion mediated by [Cp*Ir(pyza)Cl] ( 1, pyza = pyrazine amidate). 1 was designed through a rational approach aimed at lowering the overpotential of NAD + to NADH reduction with respect to that observed for electrocatalyst [Cp*Ir(pica)Cl] ( 2, pica = picolinamidate). The peculiar properties of pyza, which is substantially less σ electron-donator and more π electron-acceptor than pica, resulted in an easier bielectronic reduction process occurring at −0.29 V (instead of ca. −0.65 V for 2 ), very close to the equilibrium potential of NAD + /NADH redox couple ( E ° eq = −0.32 V vs NHE, 298 K, pH 7). 1 catalyzes both NAD + reduction and NADH oxidation in response to even a small departure from equilibrium potential, with a catalytic bias for the former (|i p red /i p ox | = 6.2, 333 K). The reversibility of NAD + /NADH interconversion was ascertained by 1 H EXSY NMR spectroscopy that clearly demonstrated the rapid establishment of 1 _H + NAD + ⇌ 1 + NADH equilibrium ( K eq = 3, Δ G = −0.6 kcal/mol, 298 K) and a similar hydridicity of NADH (28.9 kcal/mol, 298 K) and 1 _H (28.3 kcal/mol, 298 K).