Chemistry of the Diazeniumdiolates. O- versus N-Alkylation of the RNH[N(O)NO]<sup>-</sup> Ion SaavedraJoseph E. BohleD. Scott SmithKamilah N. GeorgeClifford DeschampsJeffrey R. ParrishDamon IvanicJoseph WangYan-Ni CitroMichael L. KeeferLarry K. 2004 Monomethylation of the potentially ambident RNH[N(O)NO]<sup>-</sup> ion (R = isopropyl or cyclohexyl) has been shown to occur at the terminal oxygen to yield the novel diazeniumdiolate structural unit, RNHN(O)NOMe. The NH bond of the product proved acidic, with a p<i>K</i><sub>a</sub> of 12.3 in aqueous solution. The ultraviolet spectrum showed a large bathochromic shift on ionization (λ<sub>max</sub> 244 → 284 nm, ε<sub>max</sub> 6.9 → 9.8 mM<sup>-1</sup> cm<sup>-1</sup>). Deprotonation led to a pH-dependent line broadening in the <sup>1</sup>H NMR spectrum of <i>i</i>PrNHN(O)NOMe, suggesting a complex fluxionality possibly involving isomerizations around the N−N bonds. Consistent with this interpretation, evidence for extensive delocalization and associated changes in bond order on ionizing RNHN(O)NOR‘ were found in density functional theory calculations using Gaussian 03 with B3LYP/6-311++G** basis sets. With MeNHN(O)NOMe as a model, all NN and NO bonds lengthened by 0.04−0.07 Å as a result of ionization except for the MeN−N linkage, which shortened by 7%. These anions can be N-alkylated to generate R<sup>1</sup>R<sup>2</sup>NN(O)NOR<sup>3</sup> derivatives that would otherwise be difficult to access synthetically. Additionally, some RNHN(O)NOR‘ species may display unique and beneficial pharmacological properties. As one example, an agent with R = isopropyl and R‘ = β-d-glucosyl was prepared and shown to generate nitric oxide in the presence of glucosidase at pH 5.