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

Abstract

Bis(demethoxy)curcumin (BDMC) is one of the main active components found in turmeric. Major drawbacks for its usage are its low aqueous solubility, and the challenging separation from other curcuminoids present in turmeric. Co-crystallization can be applied to alter the physicochemical properties of BDMC in a desired manner. A co-crystal screening of BDMC with four hydroxybenzenes was carried out using four different methods of co-crystal production: crystallization from solution by slow solvent evaporation (SSE), and rapid solvent removal (RSR), liquid-assisted grinding (LAG), and crystallization from the melt phase. Two co-crystal phases of BDMC were obtained with pyrogallol (PYR), and hydroxyquinol (HYQ). PYR-BDMC co-crystals can be obtained only from the melt, while HYQ-BDMC co-crystals could also be produced by LAG. Both co-crystals possess an equimolar composition and reveal an incongruent melting behavior. Infrared spectroscopy demonstrated the presence of BDMC in the diketo form in the PYR co-crystals, while it is in a more stable keto-enol form in the HYQ co-crystals. Solubility measurements in ethanol and an ethanol-water mixture revealed an increase of solubility in the latter, but a slightly negative effect on ethanol solubility. These results are useful for a prospective development of crystallization-based separation processes of chemical similar substances through co-crystallization.

Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation

“…The first enterotoxin SEA was isolated in 1959, and so far, 25 SEs (SEA-SElZ) have been described [14]. These peptides are classified as pyrogenic toxin superantigens (SAg), which can mobilize a large number of T cells [15], resulting in the release of a large number of pro-inflammatory cytokines (such as IL-6 and TNF-α), leading to toxic shock syndrome (TSS) [16]. Characterized by high fever, rash and hypertension, it can rapidly progress to multiple organ failure and death, among which, Staphylococcal enterotoxin B (SEB) is a typical enterotoxin.…”

Cocrystallization of Curcuminoids with Hydroxybenzenes Pyrogallol and Hydroxyquinol: Investigations of Binary Thermal Phase Behaviors

“…CUR can be purified from the mixture using classical and nonclassical crystallization routes. − Purification and separation of CURDs from the remaining mother liquor can be carried out by chromatography . Previous contributions (including our work) confirmed the presence of cocrystals of CUR and BDMC in a 1:1 molar composition with both trihydroxybenzenes. ,,, To the best knowledge of the authors, this is the first time that binary mixtures of DMC with PYR and HYQ have been studied. Binary phase diagrams of all systems under investigation are constructed from experimental data and compared to calculated ones using the Schroeder–van Laar and Prigogine–Defay equation, respectively.…”

“…Three solvates with 1,4-dioxane, methyl acetate, and dichloromethane and several cocrystals, e.g., with resorcinol, catechol, hydroquinone, pyrogallol, hydroxyquinol, and nicotinamide have been discovered to date. − For BDMC, only one crystal structure in the monoclinic space group P 2/ c is known . Besides that, six solvates with acetone, methanol, isopropanol, tetrahydrofuran, 1,4-dioxane, and dimethyl sulfoxide and two cocrystals with pyrogallol and hydroxyquinol were discovered. − So far, there are no crystal structure data available for DMC.…”

Effect of Co-Administration of Curcumin with Amlodipine in Hypertension

“…Curcuminoids, known as the main biologically active compounds of turmeric, consist of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which only differ in the presence of one or two methoxy groups. Curcumin accounts for 75–80% of curcuminoids [ 1 ]. Curcumin has antioxidant [ 2 , 3 ], anti-inflammatory [ 3 , 4 , 5 , 6 , 7 , 8 ], and anticancer effects [ 9 , 10 , 11 ].…”