Design, Synthesis And Study Of The Functional Mitochondrial Hydrogen Peroxide Fluorescent Probe

Mitochondria, as power factory of the living cell, have the main sources of cellular reactive oxygen species (ROS). ROS play a very important role in bio-functional processes, and some evidences have shown that it is related to aging, cancer and neurodegeneration diseases, which arouse many people’s attention.Under normal biological process, all kinds of ROS remain balanced. Hydrogen peroxide is the most common ROS in cell, and it is mainly produced by mitochondria. H2O2 regulate many biological process, and if cell was stimulated to produce excessive H2O2, it will contribute to many diseases such as heart disease, diabetes, neurodegeneration diseases and aging. So it is necessary to detect ROS. Traditional probe can only detect mitochondrial ROS, but do not have abilities to regulate mitochondrial function.Through HTS, Our group discovered Sulphuretin, a natural compound, which can significantly reduce MMP (mitochondrial membrane potential) and increase glucose consumption and lactic acid producing, suppressing the synthesis of fatty acids and cholesterol. It also have the fluorescent properties. From Sulphuretin, we then investigated its SAR, and based on its SAR, we introduce a mitochondrial targeting group TPP to Sul, and replace hydroxyl with borate switcher. In this way, we design and synthetize S7, S8, Sox7, Sox8 as functional mitochondrial targeting fluorescent probes for hydrogen peroxide. We found theses probes can reduce MMP, increase glucose consumption and lactic acid producing, causing mitochondrial autophagy, and it can also suppress oxidative stress. For the fluorescent properties, S7 has no fluorescence, but SOx7 has strong blue fluorescence, and S7 can oxidize into Sox7 in mitochondria, which result in a "light on" phenomenon. So it can detect mitochondrial H2O2. Above all we design and synthetize a series of functional mitochondrial targeting fluorescent probes for H2O2, which achieved both its mitochondrial regulation properties and H2O2 detecting properties.