Nitric oxide is a vital signaling molecule that controls blood flow and oxygenation and nitrite serves as an important reservoir for nitric oxide in biology. While copper containing enzymes are known to reduce nitrite to nitric oxide, herein we report a new pathway to release nitric oxide via oxygen atom transfer from nitrite at a copper(ii) site.

Nitric oxide (NO) is a key signaling molecule in health and disease. While nitrite acts as a reservoir of NO activity, mechanisms for NO release require further understanding. A series of electronically varied β-diketiminatocopper(II) nitrite complexes [Cu II ](κ 2 -O 2 N) react with a range of electronically tuned triarylphosphines PAr Z 3 that release NO with the formation of OPAr Z 3 . Second-order rate constants are largest for electron-poor copper(II) nitrite and electron-rich phosphine pairs. Computational analysis reveals a transition-state structure energetically matched with experimentally determined activation barriers. The production of NO follows a pathway that involves nitrite isomerization at Cu II from κ 2 -O 2 N to κ 1 -NO 2 followed by O-atom transfer (OAT) to form OPAr Z 3 and [Cu I ]-NO that releases NO upon PAr Z 3 binding at Cu I to form [Cu I ]-PAr Z 3 . These findings illustrate important mechanistic considerations involved in NO formation from nitrite via OAT.

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 [Cl₂NN_F6]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 [Cu^II](k²-O₂N) to give the copper(II) hydroxide [Cu^II]-OH along with the <i>O-</i>nitrosated phenol ArONO that ultimately leads to the corresponding biphenol or <i>o</i>-nitrophenol. The especially electron-rich antioxidant a-tocapherol (vitamin E) quickly generates NO upon interaction with [Cu^II](k²-O₂N). X-ray analysis of the oxidation products of the a-tocapherol analogue PMC reveal formation of an elusive <i>O</i>-quinone methide bound to [Cu^I], revealing two electron oxidation of PMC by [Cu^II](k²-O₂N). These studies illustrate anaerobic pathways that generate NO from nitrite at copper(II) sites that result in phenol oxidation.

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 [Cl₂NN_F6]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 [Cu^II](k²-O₂N) to give the copper(II) hydroxide [Cu^II]-OH along with the <i>O-</i>nitrosated phenol ArONO that ultimately leads to the corresponding biphenol or <i>o</i>-nitrophenol. The especially electron-rich antioxidant a-tocapherol (vitamin E) quickly generates NO upon interaction with [Cu^II](k²-O₂N). X-ray analysis of the oxidation products of the a-tocapherol analogue PMC reveal formation of an elusive <i>O</i>-quinone methide bound to [Cu^I], revealing two electron oxidation of PMC by [Cu^II](k²-O₂N). These studies illustrate anaerobic pathways that generate NO from nitrite at copper(II) sites that result in phenol oxidation.

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