Elucidating the Polymorphic Behavior of Curcumin during Antisolvent Crystallization: Insights from Raman Spectroscopy and Molecular Modeling

Abstract

The focus of this work is to understand the polymorphic behavior of curcumin crystallized from two different organic solvents by liquid antisolvent (LAS) precipitation carried out in a semibatch mode. LAS precipitation of curcumin from ethanol yielded the metastable (orthorhombic) Form 3, while acetonitrile led to the precipitation of stable (monoclinic) Form 1. These polymorphic crystal structures mirrored clustering of curcumin molecules in the respective organic solutions determined using in situ Raman spectroscopy. The presence of strong CH•••O bonds in acetonitrile solution indicated interactions between curcumin molecules through the phenolic end groups. On the other hand, parallel stacking of curcumin molecules was favored in ethanol solution due to stronger solute−solvent interactions at the polar end groups. These observations are consistent with the results obtained from density function theory (DFT) calculations and molecular dynamics (MD) simulations. Accordingly, with acetonitrile interacting weakly with the solute molecules, curcumin−curcumin interactions through the phenolic ends were promoted, in turn, favoring formation of Form 1. Stronger interaction between ethanol and curcumin led to relaxation of solute molecules into parallel stacked clusters, thereby favoring Form 3. Furthermore, the solvatochromic effect of curcumin exhibited in these solvents was related to solvent-induced conformations and, in turn, nucleation of curcumin crystal polymorphs.

Molecular Structure of Cefuroxime Axetil Complexes with α-, β-, γ-, and 2-Hydroxypropyl-β-Cyclodextrins: Molecular Simulations and Raman Spectroscopic and Imaging Studies

“…Simultaneous use of these two methods was also applied successfully by other researchers in pharmaceutical and biochemical fields. They were utilized inter alia to study the crystal structure of the chiral antiparasitic drug Praziquantel [ 74 ], examine the equilibrium geometry, bonding features, and harmonic vibrational frequencies in benzothiazole [ 75 ], investigate the polymorphic behavior of crystallized curcumin [ 76 ], explore the interaction of hypericin with serum albumins [ 77 ], and chromate with 4-(2-mercaptoethyl)pyridinium [ 78 ]. In the future, it will be possible to apply these techniques to analyze more types of active compounds in pharmaceutical formulations and guest–host complexes, leading to the design of drugs with appropriate pharmacokinetic properties, thereby increasing their bioavailability.…”

Nanofiber-mediated sequential photothermal antibacteria and macrophage polarization for healing MRSA-infected diabetic wounds

“…1 d). The peaks centered at 1579 cm −1 could be assigned to ν (C=C) aromatic coupled with pyrrole ring stretching vibration or indole ring vibration from PDA coating [ 55 ] or Cur [ 56 ], and the peak at 1355 cm −1 was due to the aromatic ν(C-N) stretching mixed with indole ring stretching from the PDA coating. These results partly represent the structural features of the monomers composing PDA [ 57 , 58 ].…”

Ketoprofen Solubility in Pure Organic Solvents Using In Situ FTIR and UV–Vis and Analysis of Solution Thermodynamics

“…This shift was particularly notable in the case of alcohols, decreasing in the order MeOH > EtOH > IPrOH > BuOH, in agreement with the decreasing order of solubility data. In the literature, a longer shift to higher wavelengths has been related to a higher propensity of hydrogen bond between the solute and solvent molecules, eventually leading to a higher solubility. In the present study, such a rule clearly applies with the order of solubility found in alcoholic solvents, EA and ACN.…”