The secondary amine/nitric oxide complex ion R2N[N(O)NO](-) as nucleophileand leaving group in SNAr reactions

Ions of structure R2N[N(O)NO](-) and their alkylation products have seen in creasing use as nitric oxide (NO)-generating agents for biomedical research applications. Were we show that such diazeniumdiolate anions can readily d isplace halide from a variety of electrophilic aza- or nitroaromatic substr ates to form O-2-arylated derivatives of structure R2N-N(O)=N=OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ra y crystallography. Displacement by various nucleophiles showed R2N[N(O)NO]( -) to be a reasonably good leaving group, with rate constants for displacem ent by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the SNAr reactions we surveyed. The Meisenheimer i ntermediate could be spectrally observed. These O-2-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nuc leocapsid protein's zinc finger assembly to eject the zinc, disrupting a st ructural motif critical to viral replication and suggesting possible utilit y in the drug discovery realm.