Nitric oxide (NO) is essential for vasodilation, respiration, and immune defense, yet its signaling and reduction mechanisms to N2O remain poorly understood.1,3 Its close relative, nitroxyl (HNO), exhibits similar, yet distinct reactivity to that of NO, but rapidly dimerizes to N₂O, making direct study challenging.2 While Fe-heme enzymes have been extensively studied for NO reduction, Cu-based pathways remain underexplored. Notably, Cu enzymes reduce NO to N₂O,3 yet no model systems exist to examine HNO as a possible intermediate.
Using synthetic models inspired by biology, our group has investigated NO reduction at Cu sites and has recently isolated and characterized a rare β-diketiminato supported {[Cu]-NO}⁻ species, stabilized by K(18-c-6). This marks the first example of a reduced metal nitrosyl at a monocopper site. Protonation generates a Cu(I) complex that readily releases HNO. Investigations into nitrosobenzene as a model for HNO binding reveal a κ1-N coordination to Cu. Moreover, DFT calculations support κ1-N coordination as the lowest energy binding mode.
Synthetic efforts will be described towards the characterization and isolation of [CuI](HNO) species. These include approaches that employ supporting ligands with pendant pyridyl bases to facilitate hydrogen bonding that can both stabilize the [Cu](HNO) species and facilitate its formation from a [CuI](NO) species through proton coupled electron transfer (PCET). These strategies will expand our understanding of Cu-HNO chemistry, bridging the gap between synthetic and biological NO reduction pathways.