5,6-Disubstituted phenanthridinium cations have a range of redox, fluorescence and biological properties. Some properties rely on phenanthridiniums intercalating into DNA, but the use of these cations as exomarkers for the reactive oxygen species (ROS), superoxide, and as inhibitors of acetylcholine esterase (AChE) do not require intercalation. A versatile modular synthesis of 5,6-disubstituted phenanthridiniums that introduces diversity by Suzuki–Miyaura coupling, imine formation and microwave-assisted cyclisation is presented. Computational modelling at the density functional theory (DFT) level reveals that the novel displacement of the aryl halide by an acyclic N-alkylimine proceeds by an S_NAr mechanism rather than electrocyclisation. It is found that the displacement of halide is concerted and there is no stable Meisenheimer intermediate, provided the calculations consistently use a polarisable solvent model and a diffuse basis set.

A high membrane potential across the mitochondrial inner membrane leads to the production of the reactive oxygen species (ROS) implicated in aging and age-related diseases. A prototypical drug for the correction of this type of mitochondrial dysfunction is presented. MitoDNP-SUM accumulates in mitochondria in response to the membrane potential due to its mitochondria-targeting alkyltriphenylphosphonium (TPP) cation and is uncaged by endogenous hydrogen peroxide to release the mitochondrial uncoupler, 2,4-dinitrophenol (DNP). DNP is known to reduce the high membrane potential responsible for the production of ROS. The approach potentially represents a general method for the delivery of drugs to the mitochondrial matrix through mitochondria targeting and H₂O₂-induced uncaging.