10.1021/ja031538i.s001 Joseph E. Saavedra Joseph E. Saavedra D. Scott Bohle D. Scott Bohle Kamilah N. Smith Kamilah N. Smith Clifford George Clifford George Jeffrey R. Deschamps Jeffrey R. Deschamps Damon Parrish Damon Parrish Joseph Ivanic Joseph Ivanic Yan-Ni Wang Yan-Ni Wang Michael L. Citro Michael L. Citro Larry K. Keefer Larry K. Keefer Chemistry of the Diazeniumdiolates. O- versus N-Alkylation of the RNH[N(O)NO]<sup>-</sup> Ion American Chemical Society 2004 p K isopropyl Ion Monomethylation theory calculations terminal oxygen 1 H NMR spectrum ionization bathochromic shift NH bond RNH NN RNHN B 3LYP basis sets bond order novel diazeniumdiolate access synthetically Gaussian 03 max nitric oxide 2004-10-13 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Chemistry_of_the_Diazeniumdiolates_O_versus_N_Alkylation_of_the_RNH_N_O_NO_sup_sup_Ion/3321010 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.