Molecular distortions in 1-nitro-9-methylacridine and 1-nitro-9-aminoacridine

Abstract

The high antitumor activity of certain 1-nitroacridines has been reported, and Ledakrin (1-nitro-9-(3-dimethylaminopropylimino)-acridine) is used clinically in Poland as an antineo-plastic agent. To investigate the role of the 1-nitro group in enhancing antitumor activity, the crystal structures of 1-nitro-9-aminoacridine and 1-nitro-9-methylacridine have been determined. 1-Nitro-9-methylacridine crystallizes in the orthorhombic space group Pbca, with Z = 8 and a = 13.822(4), b = 9.927(3), c = 17.248(6) A ̊ , V = 2217(1) A ̊ 3 . The final R value, after least-squares refinement, is 0.056, for 2155 observed intensities. The structure of 1-nitro-9-aminoacridine is approximately isomorphous with that of the 9-methyl derivative, with unit cell dimensions a = 13.217(2), b = 10.011(1), c = 16.373(1) A ̊ , V = 2166.4(5) A ̊ 3 . The final R value, after least-squares refinement, is 0.058, for 1534 observed intensities. The structures were solved independently by direct methods. The steric interference between the 1-nitro and the 9-methyl- or 9-amino-substituents on the acridine ring system causes considerable deviations from planarity in both structures. There are two possible intramolecular hydrogen bonds between the amino group and the disordered nitro group in 1-nitro-9-aminoacridine. Unlike N 9-alkyl derivatives of 1-nitroacridines that have been previously described, in the 9-amino derivative the exocyclic nitrogen adopts the amino rather than the imino form.