Oxygen-copper (II) interplay in the repair of semi-oxidized urate by quercetin bound to human serum albumin

The 1:1 complex of copper (II) and human serum albumin (HSA) slowly reacts with radiolytically generated ^•O₂^- radical-anion at a rate constant of 6.1×10₆ M_-1 s_-1. Absorbance and fluorescence spectroscopies demonstrate that addition of an equimolar portion of quercetin (QH₂) to the solution of the copper (II)-HSA complex induces a relocalization of the copper resulting in a ternary copper (II)-QH₂-HSA complex. This form of quercetin slowly oxidizes in air-saturated solutions. A 10-fold excess urate, a plasma antioxidant, cannot displace copper (II) bound to HSA. In N₂O-saturated solutions the ternary complex form of QH₂ can repair the urate radical with a rate constant of 2.7×10₆ M_-1 s_-1 by an electron transfer reaction similar to that observed in the absence of copper (II). In O₂-saturated solutions and in the absence of copper, HSA-bound QH₂ fails to repair the urate radical because of the fast competitive reaction of ^•O₂^- with urate radicals. However, addition of equimolar copper (II) restores the electron transfer from QH₂ to the urate radical. These contrasting results are tentatively explained either by an enhanced reactivity of copper (II) with ^•O₂^- in the ternary complex or by direct production of quercetin radicals via a copper-catalyzed reduction of the ^•O₂^- radicals by QH₂.