Alternating Current Voltammetry (ACV) for Quantifying Electrochemical Dimerization of NAD⁺ Biomimetics

Biomimetics of nicotinamide adenine dinucleotide (mNADH) are promising cost-effective alternatives to their natural counterpart for biosynthetic applications; however, attempts to recycle mNADH often rely on coenzymes or precious metal catalysts. Direct electrolysis is an attractive approach for recycling mNADH, but electrochemical reduction of the oxidized mimetic (mNAD + ) primarily results in the formation of an enzymatically inactive dimer. A primary focus of our research is to design synthetic analogues of NAD + and NADH that are both enzymatically active and electrochemically regenerable. We will present our recent progress utilizing alternating current voltammetry (ACV) to quantify the electrochemical dimerization of structural derivatives to NAD + , which can exceed second order rate constants of k > 10 7 M -1 s -1 . We utilize this data to elucidate structure-reactivity relationships that lead to dimerization over the preferred formation of 1,4-dihydronicotinamide in NAD + and its biomimetics, and we will describe strategies to prevent dimerization of electrochemically reduced NAD + .