Publication
Varying degrees of homostructurality in a series of cocrystals of antimalarial drug 11-azaartemisinin with salicylic acids
Publisher:
International Union of Crystallography (IUCr)
Date:
06-05-2021
DOI:
10.1107/S2053229621004460
Abstract: The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-azaartemisinin (11-Aza systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0 4,13 .0 8,13 ]hexadecan-10-one, C 15 H 23 NO 4 ) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, C 7 H 5 BrO 3 ), 4-bromo- (4-BrSalA, C 7 H 5 BrO 3 ) and 3,5-dibromosalicylic acid (3,5-Br 2 SalA, C 7 H 4 Br 2 O 3 )] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P 2 1 ) reported previously. The 5-BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4-BrSalA and 3,5-Br 2 SalA cocrystals retain the highly preserved 2 1 stacks of the molecular pairs, but these pack with a varying degree of slippage with respect to neighbouring stacks, altering the close contacts between them, and represent two potential alternative homostructural arrangements for the parent compound. Structure redeterminations of the bromosalicylic acids 5-BrSalA, 4-BrSalA and 3,5-Br 2 SalA at 100 K show that the packing efficiency of the cocrystals need not be higher than the parent coformers, based on specific-volume calculations, attributable to the strong O—H...O=C hydrogen bonds of 2.54 Å in the cocrystals.