Naphthoquinone Derivatives As Low-Potential Electron Mediators of Fad-Dependent Glucose Dehydrogenase

Flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) is rapidly emerging as an alternative glucose-oxidizing enzyme in enzymatic fuel cells (EFCs).  FAD-GDH has the benefit over its commonly used counterpart, glucose oxidase (GOx), of not undergoing the parasitic reduction of O₂ to H₂O₂, which can be troublesome in EFC applications. Additionally, the FAD cofactor has a relatively low redox potential in comparison to heme-based and PQQ-dependent enzymes, which can allow for a much higher theoretical cell potential. However, FAD-GDH is unable to facilitate rapid rates of direct electron transfer, and therefore requires a low-overpotential redox mediator to take full advantage of the low oxidation potential of its FAD cofactor.

We have prepared a range of naphthoquinone analogues that are capable of mediating electron transfer between FAD-GDH and carbon electrodes, with onset potentials ranging between -0.425 to -0.150 V (vs. SCE), at pH 7.4. Several naphthoquinone derivatives were immobilized either onto a poly(ethylenimine) backbone or directly onto the outer shell of FAD-GDH to yield a naphthoquinone redox hydrogel and a naphthoquinone-labeled FAD-GDH. Both methods demonstrated large catalytic current densities at low onset potentials. When coupled with an O₂-reducing biocathode (bilirubin oxidase, direct electron transfer-type) the glucose/O₂ EFC possessed a large open-circuit potential (OCP) of 0.864 V and was able to deliver a maximum current density of 5.4 mA cm^-2. The EFC reached its maximum power density (2.3 mW cm^-2) at 0.55 V.