Fereidouni Nazanin, Aljohani Marwah, Erxleben Andrea
School of Biological and Chemical Sciences, University of Galway, Galway H91TK33, Ireland.
Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 76971, Dammam 31441, Saudi Arabia.
Cryst Growth Des. 2025 Mar 10;25(6):1776-1784. doi: 10.1021/acs.cgd.4c01507. eCollection 2025 Mar 19.
Stacked structures with strong dispersion forces between stack neighbors often lead to anisotropic crystal growth and needlelike morphologies. The crystal structures of a new cocrystal and a molecular salt of indomethacin (IND) are reported: IND·MOA and IND·POBA·0.5HO (MOA = -methoxyaniline, POBA = 4-phenoxybenzylamine). In both structures, the IND and coformer molecules/ions are stacked and IND adopts the unusual conformation found in the α-polymorph of pure IND, resulting in a relatively short distance of about 3 Å between the methyl group and the C1'-atom of the chlorophenyl ring. While IND·MOA and IND·POBA·0.5HO both crystallize as needles like α-IND, the weaker stacking interactions of the coformer in the IND·MOA cocrystal lead to shorter and thicker needles. Amorphous IND prepared by milling recrystallizes to the stable γ-polymorph without the metastable α-form being detected. When IND is milled in the presence of 2.5 wt % MOA, the amorphous phase converts to α-IND. The effect of small amounts of the coformer on the recrystallization route is attributed to a templating effect of the cocrystal formed during milling and/or the facilitation of the conversion to the α-phase conformation.
在堆积相邻分子间具有强色散力的堆积结构通常会导致各向异性晶体生长和针状形态。本文报道了一种新的吲哚美辛（IND）共晶体和分子盐的晶体结构：IND·MOA和IND·POBA·0.5H₂O（MOA = 间甲氧基苯胺，POBA = 4-苯氧基苄胺）。在这两种结构中，IND与共形成物分子/离子相互堆积，且IND呈现出在纯IND的α-多晶型中发现的异常构象，导致甲基与氯苯环的C1'-原子之间的距离相对较短，约为3 Å。虽然IND·MOA和IND·POBA·0.5H₂O都像α-IND一样结晶成针状，但IND·MOA共晶体中共形成物较弱的堆积相互作用导致针状晶体更短、更粗。通过研磨制备的无定形IND重结晶为稳定的γ-多晶型，未检测到亚稳的α-晶型。当在2.5 wt% MOA存在下研磨IND时，无定形相转变为α-IND。少量共形成物对重结晶途径的影响归因于研磨过程中形成的共晶体的模板效应和/或向α-相构象转变的促进作用。
