NAD+ as a Hydride Donor and Reductant

Reduced nicotinamide adenine dinucleotide (NADH) can generate a ruthenium–hydride intermediate that catalyzes the reduction of O2 to H2O2, which endows it with potent anticancer properties. A catalyst that could access a Ru–H intermediate using oxidized nicotinamide adenine dinucleotide (NAD+) as the H– source, however, could draw upon a supply of reducing equivalents 1000-fold more abundant than NADH, which would enable significantly greater H2O2 production. Herein, it is demonstrated, using the reduction of ABTS•– to ABTS2–, that NAD+ can function as a reductant. Mechanistic evidence is presented that suggests a Ru–H intermediate is formed via β-hydride elimination from a ribose subunit in NAD+. The insight gained from the heretofore unknown ability of NAD+ to function as a reductant and H– donor may lead to undiscovered biological carbohydrate oxidation pathways and new chemotherapeutic strategies.