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

Abstract

Two molecular precursors to dendrimeric materials that could serve as slow and sustained NO-releasing therapeutic agents have been synthesized and characterized. N,N-Bis(2-nitrophenyl)butane-1,4-diamine, CHNO, (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,N-Bis[2-(2-nitroanilino)ethyl]-N-(2-nitrophenyl)ethane-1,2-diamine, CHNO, (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,N-bis(2-nitrophenyl)-N,N-dinitrosobutane-1,4-diamine, CHNO, (III), and N-(2-nitrophenyl)-N,N-bis{2-[(2-nitrophenyl)(nitroso)amino]ethyl}-N-nitrosoethane-1,2-diamine, CHNO, (IV), were prepared via treatment of (I) and (II), respectively, with NaNO 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.