Solvate Formation of Bis(demethoxy)curcumin: Crystal Structure Analyses and Stability Investigations

Abstract

Bis(demethoxy)curcumin (BDMC), extracted from rhizomes of the traditional herb Curcuma longa, has revealed a wide range of medicinal applications, such as antimicrobial and anticarcinogenic. Pure BDMC was obtained by recrystallization from ethanol and three BDMC solvates were identified with acetone, methanol and isopropanol. The crystal structures of pure BDMC and the solvates were resolved by single crystal X-ray diffraction. Analyses of the crystal structures and calculations of crystal packing efficiencies revealed that pure BDMC is efficiently packed. The solvents involved are not utilized to fill the void spaces in the crystal structures, but to provide effective intermolecular interactions. The stoichiometry of the three solvates obtained from single crystal data is 1:1, which is in good agreement with the gravimetric analyses. Furthermore, the desolvation process and stability of the solvates were investigated by various analytical techniques including X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, hot-stage microscopy and dynamic vapor sorption. Results show that the methanol solvate is more stable compared to the acetone and isopropanol solvates attributed to the strong hydrogen bonding network. Moreover, the desolvation process of the three solvates proceeds through a destructive-reconstructive mechanism.

A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization

“…Through the identification of robust supramolecular synthons, it is possible to select suitable coformers for co-crystallization. BDMC can exist in the β-diketone and the keto-enol form (Figure 2a) whereas only the keto-enol form can be found in crystal structures due to its higher stability [31]. With its hydroxyl, carbonyl and phenyl functional groups the following supramolecular synthons can be identified (Figure 2b): The second approach for selecting suitable coformers is based on structural resemblance to a well investigated molecule and was first introduced by Springuel et al [38].…”

“…In a patent 6 co-crystals with piperazine, caffeine, L-proline, nicotinamide, isonicotinamide and piperidine are reported but not fully proved [ 26 ]. The formation of BDMC solvates was investigated extensively by Yuan et al [ 30 , 31 ].…”

Purification of Curcumin from Ternary Extract-Similar Mixtures of Curcuminoids in a Single Crystallization Step

“…One hypothesis explaining this behavior might be incorporation of small amounts of respective alcohol molecules in the crystal structure without changing the structure type. Further, according to the known complex solid phase behavior of CUR [42][43][44][45][46][47][48] and BDMC [49,50], also the formation of a new metastable form of CUR in the three alcohols or a solvate phase from ethanol are possible explanations. Since elucidation of the CUR phase behavior was not the main focus of the present study, this issue has to be verified in future investigations.…”

Various Molecular Arrangements Leading to Different Desolvation Rates: Research on the Stability of 2,7‐Dibromo‐9H‐carbazole Solvates

“…The engagement of the solvent molecules could compensate the original vacancy of interaction force such as the imbalance of hydrogen bonds, halogen bonds, and π–π stacking, etc., [ 9,18 ] while the incorporation of solvent molecule into the gaps of the crystals would also make a more efficient packing mode, thus further affecting the stability of solvate crystals. [ 19 ] With the development of analytical technique and computer simulation technology, [ 20,21 ] researchers have made great progress in the study of intermolecular interactions on the stability of solvates. [ 2,13,22 ] For example, Yuan et al.…”

“…[ 2,13,22 ] For example, Yuan et al. [ 19 ] studied the effect of intermolecular interaction on solvate formation of bis(demethoxy)curcumin (BDMC). It was suggested that a stronger hydrogen bond network would lead to a more stable BDMC‐MeOH solvate.…”