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

Two nitro­phenyl-substituted secondary amines have been synthesized and characterized by single-crystal X-ray diffraction, 1 H NMR, IR and mass spectrometry. Following nitro­sation of the amine groups via reaction with NaNO 2 , NO release was measured for each compound over time and the results gauged against the number of NO-donor sites. Two mol­ecular precursors to dendrimeric materials that could serve as slow and sustained NO-releasing therapeutic agents have been synthesized and characterized. N 1 , N 4 -Bis(2-nitro­phen­yl)butane-1,4-di­amine, C 16 H 18 N 4 O 4 , (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. N 2 , N 2 -Bis­[2-(2-nitroanilino)­eth­yl]- N 1 -(2-nitro­phen­yl)ethane-1,2-di­amine, C 24 H 27 N 7 O 6 , (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 N 1 , N 4 -bis­(2-nitro­phen­yl)- N 1 , N 4 -di­nitroso­butane-1,4-di­amine, C 16 H 16 N 6 O 6 , (III), and N 1 -(2-nitro­phen­yl)- N 2 , N 2 -bis­{2-[(2-nitro­phen­yl)(nitroso)amino]­eth­yl}- N 1 -nitroso­ethane-1,2-di­amine, C 24 H 24 N 10 O 9 , (IV), were prepared via treatment of (I) and (II), respectively, with NaNO 2 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.