Identification of Novel Hydroxyl-Benzoquinones as Redox Switchable Calcium Chelators and Potent Biological Antioxidants

Quinones have important functions in many vital biological processes. We have previously reported novel hydroxylated-quinone structures with a high Ca2+-binding affinity and a putatively high antioxidant capability. However, the molecular mechanisms of the chemical reactions and the physiological significance were not resolved. Here, we analyze the physiologically relevant 2,6-dimethoxy-1,4-benzoquinone (BQ), which is found in wheat and thus part of a everyday diet, but also a precursor in coenzyme Q biosynthesis. We show that BQ can be transformed into novel hydroxyl-benzoquinone forms (OHBQ) and unmask the molecular nature of the chemical reactions. Importantly, the novel OHBQ forms are very stable under physiological conditions and scavenge superoxide radicals formed by primary human monocytes with very high efficiency. Its antioxidant and Ca2+-binding properties can be switched in a redox-dependent manner. The insights into the molecular mechanism of the quinone transformation should increase their usage as powerful antioxidants and facilitate their pharmacological potential.