Saavedra Joseph E, Bohle D Scott, Smith Kamilah N, George Clifford, Deschamps Jeffrey R, Parrish Damon, Ivanic Joseph, Wang Yan-Ni, Citro Michael L, Keefer Larry K
Contribution from the Basic Research Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
J Am Chem Soc. 2004 Oct 13;126(40):12880-7. doi: 10.1021/ja031538i.
Monomethylation of the potentially ambident RNHN(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.
已证明，潜在的两可性RNHN(O)NO离子（R = 异丙基或环己基）的单甲基化发生在末端氧原子上，生成新型的二氮烯二醇盐结构单元RNHN(O)=NOMe。产物的NH键具有酸性，在水溶液中的pK(a)为12.3。紫外光谱显示电离时出现较大的红移（λ(max) 244 → 284 nm，ε(max) 6.9 → 9.8 mM(-1) cm(-1)）。去质子化导致iPrNHN(O)=NOMe的(1)H NMR谱中出现pH依赖性的谱线展宽，这表明可能存在复杂的分子内重排，可能涉及围绕N-N键的异构化。与该解释一致的是，在使用高斯03和B3LYP/6-311++G基组的密度泛函理论计算中，发现了RNHN(O)=NOR'电离时广泛离域以及键级相关变化的证据。以MeNHN(O)=NOMe为模型，除MeN-N键缩短7%外，所有N-N和N-O键因电离而延长0.04 - 0.07 Å。这些阴离子可进行N-烷基化反应，生成R(1)R(2)NN(O)=NOR(3)衍生物，否则这些衍生物很难通过合成方法得到。此外，一些RNHN(O)=NOR'物种可能具有独特且有益的药理性质。例如，制备了一种R = 异丙基且R' = β-D-葡萄糖基的试剂，结果表明该试剂在pH 5的条件下，在存在葡糖苷酶的情况下能够产生一氧化氮。
