Nitrite-Phenol-NO Crosstalk: Phenol Oxidation and NO Generation from Nitrite at Copper(II) Sites

Nitrite is involved in a plethora of biological phenomena that includes tyrosine nitration associated with neurodegenerative disorders and gastric phenol metabolism. Reaction of the b-diketiminato model complex [Cl2NNF6]Cu(k2-O2N) with phenols outlines the coupled generation of NO with phenol oxidation by nitrite at copper(II). Kinetic studies support nucleophilic attack of the hydroxyl group of phenols ArOH on the bound nitrite in [CuII](k2-O2N) to give the copper(II) hydroxide [CuII]-OH along with the O-nitrosated phenol ArONO that ultimately leads to the corresponding biphenol or o-nitrophenol. The especially electron-rich antioxidant a-tocapherol (vitamin E) quickly generates NO upon interaction with [CuII](k2-O2N). X-ray analysis of the oxidation products of the a-tocapherol analogue PMC reveal formation of an elusive O-quinone methide bound to [CuI], revealing two electron oxidation of PMC by [CuII](k2-O2N). These studies illustrate anaerobic pathways that generate NO from nitrite at copper(II) sites that result in phenol oxidation.