Structure of the antimalarial halofantrine hydrochloride.

1,3-Dichloro-alpha-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9- phenanthrenemethanol hydrochloride, C26H31Cl2F3NO+.Cl-, Mr = 536.9, monoclinic, P21/n, alpha = 8.169 (3), b = 32.924 (13), c = 22.775 (6) A, beta = 98.99 (3) degrees, V = 6050.2 A3, Z = 8, Dx = 1.18 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 15.51 cm-1, F(000) = 2240, room temperature, final R = 18.3% for 2899 reflections with [Fo] greater than 3 sigma. The crystal structure of halofantrine hydrochloride was determined to 1.0 to 1.1 A resolution. The high R factor is due to poor crystal quality. In order to have a crystal with sufficient thickness for data collection, it was necessary to use a crystal that had grown in layers. The high R factor is also due to a disordered CF3 group, a disordered solvent channel, and high thermal factors on the long hydrocarbon chains. The two halofantrine conformers stack such that the phenanthrene rings are nearly on top of each other with the chlorine and CF3 groups on opposite sides and with the hydrocarbon side chains projected away from each other, but on the same side of the phenanthrene rings. Atoms in the phenanthrene rings of the two stacked conformers are separated by 3.4 to 3.7 A. On each of the halofantrine conformers, one of the n-butyl groups extends in a linear fashion whereas the other n-butyl group is bent back towards the phenanthrene ring.(ABSTRACT TRUNCATED AT 250 WORDS)