Mechanism of O-Atom Transfer from Nitrite: Nitric Oxide Release at Copper(II)

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](κ²-O₂N) react with a range of electronically tuned triarylphosphines PAr^Z₃ that release NO with the formation of O═PAr^Z₃. 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 κ²-O₂N to κ¹-NO₂ followed by O-atom transfer (OAT) to form O═PAr^Z₃ and [Cu^I]-NO that releases NO upon PAr^Z₃ binding at Cu^I to form [Cu^I]-PAr^Z₃. These findings illustrate important mechanistic considerations involved in NO formation from nitrite via OAT.