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

• Published in: Acta crystallographica. Section C, Crystal structure communications Crystal structure communications, 2018-09, Vol.74 (9), p.1038-1044
• Main Authors: Badour, Alec R., Arnett-Butscher, Corey J., Mohanty, Dillip K., Squattrito, Philip J., Lambright, Kelly J., Kirschbaum, Kristin
• Format: Article
• Language: English
• Subjects: Acetic acid; Amines - chemistry; Chemical bonds; Chemical compounds; Crystal structure; Crystallography, X-Ray; dendritic material; Dendritic structure; Diamines - chemistry; Dimers; Donors (electronic); Ethane; Hydrogen Bonding; Hydrogen bonds; Molecular conformation; Molecular Structure; Nitric oxide; nitric oxide donor; Nitric Oxide Donors - chemistry; nitrosated derivatives; NO release; Organic chemistry; Pharmacology; Precursors; Release agents; Sodium nitrite
• ISSN: 2053-2296; 0108-2701; 2053-2296; 1600-5759
• DOI: 10.1107/S2053229618011737

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, C16H18N4O4, (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‐diamine, C24H27N7O6, (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, C16H16N6O6, (III), and N1‐(2‐nitrophenyl)‐N2,N2‐bis{2‐[(2‐nitrophenyl)(nitroso)amino]ethyl}‐N1‐nitrosoethane‐1,2‐diamine, C24H24N10O9, (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. Two nitrophenyl‐substituted secondary amines have been synthesized and characterized by single‐crystal X‐ray diffraction, 1H NMR, IR and mass spectrometry. Following nitrosation of the amine groups via reaction with NaNO2, NO release was measured for each compound over time and the results gauged against the number of NO‐donor sites.