This paper focuses on fundamental concepts derived from the technical evolution of organic electrochemistry that have helped us to develop sensors for the chemistry of genotoxicity, which is essentially the damage of DNA by chemicals and their metabolites. This research is driven by the need to screen for the possibility of genotoxicity of new environmental chemicals and drug candidates, about 30% of which have toxicity issues that do not manifest until clinical trials on humans. A major issue is metabolic chemistry driven mainly by cytochrome (cyt) P450s and other metabolic enzymes. Metabolic chemistry involves catalysis of organic reactions, oxidations in the case of cyt P450s. We found ways to inject electrons into cyt P450s in thin films via their native reductase electron-transfer partners to catalyze metabolic reactions electrochemically via mechanisms that are the same as in our livers. This is organic electrochemistry.

For the sensors, we needed a way to detect the resulting metabolite-related DNA damage in sensors combining thin LbL films of metabolic enzymes and DNA in which the metabolites are generated and react with DNA. We found that guanines in DNA chains can react in an electrocatalytic process involving a Ru metallopolymer (RuPVP) and provide a strong visible light output via electrochemiluminescence (ECL). This electrocatalytic process oxidizes Ru^II in the polymer to Ru^III to oxidize guanine moieties in the DNA, and a complex redox reaction sequence produces the light. The catalytic oxidation current can also be measured. Organic electro-oxidations are responsible for these outputs. Similar approaches can be used to design sensor arrays that monitor DNA oxidation.

Electrocatalytic Cyt P450 oxidations and ECL generation are combined in our most sophisticated genotoxicity sensor arrays. When DNA is damaged, its double-stranded structure is disrupted and Ru^III sites in the film gain better access to guanine moieties to produce more ECL light, or more catalytic current. Examples, including the genotoxic potential of e-cigarettes, will be discussed.