Pure Curcumin Spherulites from Impure Solutions via Nonclassical Crystallization

K Vasanth Kumar; Kiran A Ramisetty; K Renuka Devi; Gamidi Rama Krishna; Claire Heffernan; Andrew A Stewart; Jian Guo; Srinivas Gadipelli; Dan J L Brett; Evangelos P Favvas; Åke C Rasmuson

doi:10.1021/acsomega.1c02794

Pure Curcumin Spherulites from Impure Solutions via Nonclassical Crystallization

ACS Omega. 2021 Sep 2;6(37):23884-23900. doi: 10.1021/acsomega.1c02794. eCollection 2021 Sep 21.

Affiliations

¹ Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences and the Bernal Institute, University of LimerickRINGGOLD, Limerick V94 T9PX, Ireland.
² Department of Physics and the Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
³ Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, U.K.
⁴ Electrochemical Innovation Lab, Department of Chemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
⁵ Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", Agia Paraskevi 15341, Attica, Greece.

Abstract

Crystallization experiments performed with highly supercooled solutions produced highly pure (>99 wt %) and highly crystalline mesocrystals of curcumin from impure solutions (∼22% of two structurally similar impurities) in one step. These mesocrystals exhibited a crystallographic hierarchy and were composed of perfectly or imperfectly aligned nanometer-thick crystallites. X-ray diffraction and spectroscopic analysis confirmed that the spherulites are a new solid form of curcumin. A theoretical hypothesis based on particle aggregation, double nucleation, and repeated secondary nucleation is proposed to explain the spherulite formation mechanism. The experimental results provide, for the first time, evidence for an organic molecule to naturally form spherulites without the presence of any stabilizing agents. Control experiments performed with highly supercooled pure solutions produced spherulites, confirming that the formation of spherulites is attributed to the high degree of supercooling and not due to the presence of impurities. Likewise, control experiments performed with a lower degree of supercooling produced impure crystals of curcumin via classical molecular addition mechanisms. Collectively, these experimental observations provide, for the first time, evidence for particle-mediated crystallization as an alternate and efficient method to purify organic compounds.