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 pK(a) of 12.3 in aqueous solution. The ultraviolet spectrum showed a large bathochromic shift on ionization (lambda(max) 244 --> 284 nm, epsilon(max) 6.9 --> 9.8 mM(-1) cm(-1)). Deprotonation led to a pH-dependent line broadening in the (1)H 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 A as a result of ionization except for the MeN-N linkage, which shortened by 7%. These anions can be N-alkylated to generate R(1)R(2)NN(O)=NOR(3) 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' = beta-D-glucosyl was prepared and shown to generate nitric oxide in the presence of glucosidase at pH 5.