Interaction of 6-Bromo- and 6-Chloro-Ubiquinone derivatives with mitochondrial electron transfer system

To understand the reaction mechanism of quinone-mediated electron transfer, a series of ubiquinone (Q)-derivatives with a bromine or chlorine atom at the 6-position and a different alkyl side chains at the 5-position of the benzoquinone ring were synthesized and characterized. The chemical properties and electron transfer activities were compared with the native ubiquinone, Q0C10. The redox midpoint potential of 6-Bromo- and 6-chloro-Q derivatives is 142 mV and 148 mV, respectively. These 6-halo-Q derivatives are reducible by ascorbate alone or by succinate in the presence of succinate-ubiquinone reductase. The reduced 6-halo-Q (6-halo-QH2) can be oxidized by cytochrome c alone or via ubiquinol-cytochrome c reductase. In the presence of cytochrome c oxidase and cytochrome c, 6-halo-QH2 is oxidizable by oxygen. 6-Halo-Q derivatives are reducible by succinate via succinate-ubiquinone reductase. They function as an electron-mediator connecting succinate-Q reductase and cytochrome c oxidase and bypass ubiquinol-cytochrome c reductase in the mitochondrial electron-transfer chain. This bypassing results in a decrease in energy coupling efficiency and a lower P/O ratio. These compounds might have therapeutic value in treating diseases that are caused by the oversupply of energy.