Chemistry of the Diazeniumdiolates. O- versus N-Alkylation of the RNH[N(O)NO]- Ion

Monomethylation of the potentially ambident RNH[N(O)NO]- 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 pKa of 12.3 in aqueous solution. The ultraviolet spectrum showed a large bathochromic shift on ionization (λmax 244 → 284 nm, εmax 6.9 → 9.8 mM-1 cm-1). Deprotonation led to a pH-dependent line broadening in the 1H NMR spectrum of iPrNHN(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 R1R2NN(O)NOR3 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.