Models for potential dendritic nitric oxide donors: Crystal structures of two 2-nitroanilino precursors and nitric oxide-release behavior of the nitrosated derivatives

Two molecular precursors to dendrimeric materials that could serve as slow and sustained NO-releasing therapeutic agents have been synthesized and characterized. N¹,N⁴-Bis(2-nitrophenyl)butane-1,4-diamine, C₁₆ H₁₈N₄O₄, (I), crystallizes in a lattice with equal populations of two molecules of different conformations, both of which possess inversion symmetry through the central C—C bond. One molecule has exclusively anti conformations along the butyl chain, while the other has a gauche conformation of the substituents on the first C—C bond. N²,N²-Bis[2-(2-nitroanilino)ethyl]-N¹-(2-nitrophenyl)ethane-1,2-di-amine, C₂₄ H₂₇N₇O₆, (II), crystallizes with one unique molecule in the asymmetric unit. Neighboring pairs of molecules are linked into dimers via N—H…O amine–nitro hydrogen bonds. The dimers are assembled into layers that stack in an A–B–A–B sequence such that the repeat distance in the stacking direction is over 46 Å. Molecular NO-release agents N¹,N⁴-bis(2-nitrophenyl)-N¹,N⁴-dinitrosobutane-1,4-diamine, C₁₆ H₁₆N₆O₆, (III), and N¹-(2-nitrophenyl)-N²,N²-bis{2-[(2-nitrophenyl)(nitroso)amino]ethyl}-N¹-nitrosoethane-1,2-diamine, C₂₄ H₂₄ N₁₀ O₉, (IV), were prepared via treatment of (I) and (II), respectively, with NaNO₂ and acetic acid. The release of NO from solid-phase samples of (III) and (IV) suspended in phosphate buffer was monitored spectroscopically over a period of 21 days. Although (IV) released a greater amount of NO, as expected due to it having three NO moieties for every two in (III), the (IV):(III) ratio of the rate and extent of NO release was significantly less than 1.5:1, suggesting that some combination of electronic, chemical, and/or steric factors may be affecting the release process.