TY - JOUR
T1 - Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry
AU - Nisar, Madiha
AU - Wong, Lawrence W.Y.
AU - Sung, Herman H.Y.
AU - Haynes, Richard K.
AU - Williams, Ian D.
N1 - Publisher Copyright:
© 2018 International Union of Crystallography.
PY - 2018
Y1 - 2018
N2 - The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) 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) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C15H23NO4·C9H8O2). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C15H23NO4·C4H4O4), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza2:Mal (3, 2C15H23NO4·C4H4O4). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza2:Fum (4). All cocrystal formation appears driven by acid-lactam R22(8) heterosynthons with short O-H…O=C hydrogen bonds [O…O = 2.56 (2) Å], augmented by weaker C=O…H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.
AB - The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) 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) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C15H23NO4·C9H8O2). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C15H23NO4·C4H4O4), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza2:Mal (3, 2C15H23NO4·C4H4O4). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza2:Fum (4). All cocrystal formation appears driven by acid-lactam R22(8) heterosynthons with short O-H…O=C hydrogen bonds [O…O = 2.56 (2) Å], augmented by weaker C=O…H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.
KW - Antimalarial
KW - Artemisinin
KW - Cocrystals
KW - Crystal structure
KW - GRAS compound
KW - Lactam-acid synthon
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U2 - 10.1107/S2053229618006320
DO - 10.1107/S2053229618006320
M3 - Article
C2 - 29870011
AN - SCOPUS:85048298179
SN - 0108-2701
VL - 74
SP - 742
EP - 751
JO - Acta Crystallographica Section C: Structural Chemistry
JF - Acta Crystallographica Section C: Structural Chemistry
ER -