Surface-modified electrodes in the mimicry of oxidative drug metabolism

•Surface-modified electrodes can mimic Phase-I metabolic reactions.•Self-assembly monolayers support immobilization of Cytochrome P450 enzymes.•Electropolymerized pyrrole-monosubstituted manganese tetraphenylporphyrins.•Carbon nanomaterials are suitable for Cytochrome P450 inhibitor screening.

This review discusses different approaches that have been taken to mimic oxidative drug metabolism as executed by members of the Cytochrome P450 (CYP450) family of enzymes in humans. Non-modified electrodes can be used to produce some of the oxidative drug metabolites observed in vivo but their scope is rather limited. Modifying electrodes with simple cofactors in analogy to those observed in CYP450 but without the protein scaffold extends these possibilities and notably allows driving reactions following a CYP450-like mechanism. The review ends with approaches to immobilize CYP450s or analogs thereof on electrodes to mimic the in vivo drug metabolism fully. We discuss future perspectives with respect to the advantages and the disadvantages of each level of complexity and possible ways forward.