The secondary amine/nitric oxide complex ion R₂N[N(O)NO]^- as nucleophile and leaving group in S_NAr reactions

Ions of structure R₂N[N(O)NO]^- and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety of electrophilic aza- or nitroaromatic substrates to form O²-arylated derivatives of structure R₂N-N(O)=N-OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R₂N[N(O)NO]^- to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the S_NAr reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These O²-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly to eject the zinc, disrupting a structural motif critical to viral replication and suggesting possible utility in the drug discovery realm.