Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW O } Determined by Single-Cell Proteomics Analysis.

The 10-nuclear heteroatom cluster modified {SbW O } was successfully synthesized and exhibited inhibitory activity (IC =0.29 μM). Based on proteomics analysis, Na Ni Sb W -SbW inhibited ATP production by affecting the expression of 16 related proteins, hindering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress. In particular, the low expression of FAD/FMN-binding redox enzymes (relative expression ratio of the experimental group to the control=0.43843) could be attributed to the redox mechanism of Na Ni Sb W -SbW , which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na Ni Sb W -SbW combined with FMN to form Na Ni Sb W -SbW -2FMN complex through a one-electron process of the W atoms. Na Ni Sb W -SbW acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 μM of NADPH and 86.06 % at 10.62 μM of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.