TY - JOUR
T1 - Varying degrees of homostructurality in a series of cocrystals of antimalarial drug 11-azaartemisinin with salicylic acids
AU - Roy, Monalisa
AU - Li, Keyao
AU - Nisar, Madiha
AU - Wong, Lawrence W.Y.
AU - Sung, Herman H.Y.
AU - Haynes, Richard K.
AU - Williams, Ian D.
N1 - Publisher Copyright:
© 2021 EDP Sciences. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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-tetra-cyclo-[10.3.1.04,13.08,13]hexa-decan-10-one, C15H23NO4) with bromo-substituted salicylic acids [namely, 5-bromo-(5-BrSalA, C7H5BrO3), 4-bromo-(4-BrSalA, C7H5BrO3) and 3,5-di-bromo-salicylic 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 mol-ecular 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 com-pound. Structure redeterminations of the bromo-salicylic 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 A˚ in the cocrystals.
AB - 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-tetra-cyclo-[10.3.1.04,13.08,13]hexa-decan-10-one, C15H23NO4) with bromo-substituted salicylic acids [namely, 5-bromo-(5-BrSalA, C7H5BrO3), 4-bromo-(4-BrSalA, C7H5BrO3) and 3,5-di-bromo-salicylic 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 mol-ecular 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 com-pound. Structure redeterminations of the bromo-salicylic 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 A˚ in the cocrystals.
KW - 11-aza-artemisinin
KW - anti-malarial
KW - bromo-salicylic acid
KW - cocrystal
KW - crystal structure
KW - hetero-seeding
KW - homostructural
KW - isostructural
KW - polymorph
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U2 - 10.1107/S2053229621004460
DO - 10.1107/S2053229621004460
M3 - Article
C2 - 34089249
AN - SCOPUS:85107902908
SN - 0108-2701
VL - 77
SP - 262
EP - 270
JO - Acta Crystallographica Section C: Structural Chemistry
JF - Acta Crystallographica Section C: Structural Chemistry
ER -