Low Temperature X-Ray Crystallographic Structure of the Antiplasmodial Compound 5-N-Hydroxyethanequindoline Hydrochloride 0.5CH3OH

• Published in: Journal of chemical crystallography 2011-11, Vol.41 (11), p.1757-1762
• Main Authors: Hampson, Hannah C., Ho, Chung Y., Palmer, Rex A., Potter, Brian S., Helliwell, Madeleine, Wright, Colin W.
• Format: Article
• Language: English
• Subjects: Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Inorganic Chemistry; Organometallic Chemistry; Original Paper; Physical Chemistry
• ISSN: 1074-1542; 1572-8854
• DOI: 10.1007/s10870-011-0169-5

The structure of 5- N -hydroxyethanequindoline hydrochloride methanolate, C 17 H 15 ON 2 Cl · ½CH 3 OH, M r  = 314.78, has been determined from X-ray diffraction data. The crystals are monoclinic, space group C 2/ c, with Z  = 8 molecules per unit cell and a  = 18.179(11), b  = 7.317(5), c  = 24.125(15) Å, β = 110.155(10)°, V c  = 3012(3) Å 3 , crystal density D c  = 1.388 Mg m −3 . The structure was solved by direct methods, and the asymmetric unit comprises the 5- N -hydroxyethanequindoline hydrochloride and ½CH 3 OH moiety. The methanol is unusually disordered over a twofold axis with the C atom slightly removed from the twofold axis. Restraints were applied to the bond lengths of the two components of the disordered CH 3 OH, and to the anisotropic thermal displacement parameters of the disordered CH 3 OH carbon atom. The heterocyclic quindoline ring system and the first C atom of the hydroxyethane side chain are planar within 0.02 Å, with the terminal C–OH atoms of the side chain significantly out of the plane. The crystal structure is maintained via three hydrogen bonds all involving the chlorine atom an oxygen in the hydroxyethane side chain, a nitrogen in the quindoline moiety and the methanol oxygen. Graphical Abstract The novel cryptolepine analogue, 5- N -hydroxyethanequindoline was synthesised as part of an ongoing exploration of cryptolepine analogues as lead compounds towards antimalarial and anticancer agents. In previous work it has been shown that halogen ring substituents enhance the antimalarial properties of cryptolepine and improve its selectivity but the effects of modification of the 5- N substituent on antiplasmodial activity has not so far been investigated. Although, the antiplasmodial activity of this analogue was found to be less than that of cryptolepine, the X-ray structure of this compound will help to determine whether or not 5- N -hydroxyethanequindoline is able to intercalate into DNA and facilitate the design of new cryptolepine analogues with DNA binding properties appropriate for antimalarial (with no DNA intercalation) or anticancer (sequence-specific binding) applications.