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.

Copper nitrite reductases (CuNIRs) convert NO 2 − to NO as well as NO to N 2 O under high NO flux at a mononuclear type 2 Cu center. While model complexes illustrate N−N coupling from NO that results in symmetric trans-hyponitrite [Cu II ]− ONNO−[Cu II ] complexes, we report NO assembly at a single Cu site in the presence of an external reductant Cp* 2 M (M = Co, Fe) to give the first copper cis-hyponitrites [Cp* 2 M]{[Cu II ](κ 2 -O 2 N 2 )[Cu I ]}. Importantly, the κ 1 −N-bound [Cu I ] fragment may be easily removed by the addition of mild Lewis bases such as CNAr or pyridine to form the spectroscopically similar anion {[Cu II ](κ 2 -O 2 N 2 )} − . The addition of electrophiles such as H + to these anionic copper(II) cis-hyponitrites leads to N 2 O generation with the formation of the dicopper(II)-bis-μ-hydroxide [Cu II ] 2 (μ-OH) 2 . One-electron oxidation of the {[Cu II ](κ 2 -O 2 N 2 )} − core turns on H-atom transfer reactivity, enabling the oxidation of 9,10dihydroanthracene to anthracene with concomitant formation of N 2 O and [Cu II ] 2 (μ-OH) 2 . These studies illustrate both the reductive coupling of NO at a single copper center and a way to harness the strong oxidizing power of nitric oxide via the neutral cishyponitrite [Cu](κ 2 -O 2 N 2 ).

Reduction of nitrate is an essential, yet challenging chemical task required to manage this relatively inert oxoanion in the environment and biology. We show that thiols, ubiquitous reductants in biology, convert nitrate to nitric oxide at a Cu(II) center under mild conditions. The β-diketiminato complex [Cl 2 NN F6 ]Cu(κ 2 -O 2 NO) engages in O-atom transfer with various thiols (RSH) to form the corresponding copper(II) nitrite [Cu II ](κ 2 -O 2 N) and sulfenic acid (RSOH). The copper(II) nitrite further reacts with RSH to give S-nitrosothiols RSNO and [Cu II ] 2 (μ-OH) 2 en route to NO formation via [Cu II ]-SR intermediates. The gasotransmitter H 2 S also reduces nitrate at copper(II) to generate NO, providing a lens into NO 3 − /H 2 S crosstalk. The interaction of thiols with nitrate at copper(II) releases a cascade of N-and S-based signaling molecules in biology. Article pubs.acs.org/JACS