Evaluation of electrocatalysis of hourglass-shaped polyoxometallates with different transition metals towards hydrogen peroxide transformed from superoxide radicals in living cell mitochondria

In this work, we study the electrocatalytic detection of H 2 O 2 at electrodes correspondingly modified by four hourglass-shaped polyoxometallates (POMs) with Cu, Co, Mn and Cs as their individual central metal atoms, and four representative Wells-Dawson POMs with the same metal atoms. In this way, we have related their analytical performance to the open structures of hourglass-shaped POMs and the cage-like structures of Wells-Dawson POMs. Among them, we found the three-dimensional hourglass phosphomolybdate (POM 1 ) with plentiful exposed Cu active sites exhibits a dynamic range of 0.1–10 μM, a sensitivity of 11.6 μA μM −1  cm −2 , and a limit of detection as low as 44 nM for H 2 O 2 . It also offers high selectivity, fast response time (2 s), a reproducibility of  ∼1.69% and retains  ∼97.9% of the initial current after 15 days, verifying its good stability. Accordingly, the POM 1 -modified electrode was applied to monitoring H 2 O 2 converted from superoxide anion radical (O 2 − ) generated by mitochondria isolated and purified from human liver cancer cells (HepG2) without pharmaceutical stimulation. Meanwhile, by exploiting four specific inhibitors (rotenone, 2-thenoyltrifluoroacetone, antimycin A and paclitaxel) known to bind with targeted sites in the corresponding complex within mitochondria to produce a high H 2 O 2 concentration, our results indicated that O 2 − was mainly produced by mitochondrial complex I (ubiquinone oxidoreductase) via electron leakage in the mitochondrial electron transport chain of liver cancer. The electrochemical detection strategy in our work has provided a direct insight into the electron leakage of mitochondrial complexes caused by targeted oxidative stress diseases.