Solid-State ¹H, ¹³C, and ¹⁷O NMR Characterization of the Two Uncommon Polymorphs of Curcumin

Abstract

Curcumin is known to exist in three polymorphs (forms I, II, and III) in the solid state. The most common polymorph of curcumin (form I) is monoclinic in the space group P2/n, whereas the other two uncommon forms are both orthorhombic with the space groups of Pca21 and Pbca for forms II and III, respectively. While crystal structures are known for all three polymorphs of curcumin, their solid-state NMR signatures are incomplete in the literature. In this study, we report a complete set of solid-state 1H, 13C, and 17O NMR data for form III of curcumin. In addition, we discovered that form III of curcumin prepared by repeated drying from methanol is not stable, which undergoes slow structural transition to form II in the solid state over a period of days at room temperature. As a result, we were able to obtain new solid-state 17O NMR data for form II of curcumin, which complements the existing solid-state 1H and 13C NMR data for this polymorph in the literature. We compare experimental NMR parameters with calculated values by the GIPAW DFT and dispersion corrected DFT-D2 methods. We found that while the computed 13C chemical shifts are generally in excellent agreement with experimental values, the quality of the computed 1H and 17O NMR chemical shifts is less satisfactory. This may imply that it is necessary to include the nuclear quantum effects in future quantum chemical calculations to account for potential proton tunneling and dynamics.

Hybrid Synthetic and Computational Study of an Optimized, Solvent-Free Approach to Curcuminoids

“…To the best of our knowledge, there have been no efforts reported on the investigation of polymorphism of curcuminoids. 40 …”

“…Physical properties, including, but not limited to, solubility and melting point (two pharmaceutically important physical properties) can vary, sometimes widely, for related polymorphs. The polymorphism of curcumin specifically has been well studied, − and, furthermore, the effect of polymorphism on the melting point of curcumin has been clearly described . The range of workup procedures (e.g., columns, solvents, temperatures, etc.)…”

“…While technically correct, this could serve as an explanation for the wide range in reported melting points for some curcuminoids. To the best of our knowledge, there have been no efforts reported on the investigation of polymorphism of curcuminoids …”

Looking into the dynamics of molecular crystals of ibuprofen and terephthalic acid using 17O and 2H nuclear magnetic resonance analyses

“…[17][18][19][20][21] When it comes to studying dynamics in materials involving small organic molecules, 2 H and 17 O are both attractive quadrupolar nuclei. [22][23][24][25][26][27][28][29] This is notably true in crystals composed of molecules with carboxylic acid groups associated as dimers. Indeed, the dynamics of protons « hopping » between the H-bonded C=O and C-OH groups have been the object of much research, including using 2 H and 17 O magnetic resonance techniques.…”

Curcumin-Functionalized Gelatin Films: Antioxidant Materials with Modulated Physico-Chemical Properties

“…Curcumin—(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione—is a natural polyphenol extracted from the rhizomatous plant Curcuma Longa (Turmeric) of the Ginger family [ 1 ] ( Figure 1 ). In solution it exhibits a keto-enol tautomerism and shows polymorphism in the solid state, where it exists just as the keto-enol tautomer [ 2 ].…”