Varying degrees of homostructurality in a series of cocrystals of antimalarial drug 11-azaartemisinin with salicylic acids

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[10.3.1.04,13.08,13]hexa­decan-10-one, C15H23NO4) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, C7H5BrO3), 4-bromo- (4-BrSalA, C7H5BrO3) and 3,5-di­bromo­salicylic acid (3,5-Br2SalA, C7H4Br2O3)] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P21) reported previously. The 5-BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4-BrSalA and 3,5-Br2SalA cocrystals retain the highly preserved 21 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-Br2SalA 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.