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

摘要

The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-aza-artemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-aza-tetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-one, C15H23NO4) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, C7H5BrO3), 4-bromo- (4-Br-SalA, C7H5BrO3) and 3,5-dibromosalicylic acid (3,5-Br(2)SalA, C7H4Br2O3)] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P2(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 center dot center dot center dot O=C hydrogen bonds of 2.54 angstrom in the cocrystals.