Polymorphism in oxyresveratrol studied by 3D ED

Abstract

The polymorphism of oxyresveratrol, a natural extract widely used in traditional Asian medicine, was investigated by means of the most recent structure characterization techniques. A previously unknown anhydrate oxyresveratrol crystal structure was identified for the first time from a submicrometric polyphasic mixture using 3D electron diffraction (3D ED). Additionally, a new polymorph of the dihydrate form of oxyresveratrol was also discovered and structurally studied. Detailed thermal and calorimetry studies revealed their thermal behavior and dehydration path. DFT calculations were also employed to investigate the stability of the rotational conformers involved in the hydrated phases (in both new and already known phases). This research exemplifies how 3D ED combined with cryo-plunging and routine solid-state analysis can elucidate the polymorphism scenario of a nanocrystalline natural compound.

Figure 1

Molecular structure of oxyresveratrol (ORV). The structure is shown with the atomic labeling adopted in the paper.

Figure 2

Reconstruction of the reciprocal space of A-ORV view along the a* reciprocal direction. The arrows highlight the extinctions corresponding to the reflection condition h0l:l = 2n characteristic to a c glide plane perpendicular to b. In the box at the top left is displayed a HAADF-STEM image of typical crystals of A-ORV used for 3D ED data collection.

Figure 3

Crystal structure of A-ORV view along a, b axes and along [401] direction. In the view along b, the staggered configuration of the two chain systems is clearly visible. If the structure is viewed along [401] the interpenetration of the two chain systems can be seen. In the figure three chain layers running along [401] are displayed (indicated by light blue arrows) alternated with two layers of chains running along [−401]. Color code: brown C, red O, white H.

Figure 4

Reconstruction of the reciprocal space of H-ORV view along the a* reciprocal direction. The arrows highlight the extinctions corresponding to reflection condition h0l:l = 2n. In the box at the top left is displayed a HAADF-STEM image of typical crystals of H-ORV used for 3D ED data collection.

Figure 5

Profile fit from Rietveld refinement on PXRD data of H-ORV. The shown range is limited to 2θ values of 5–70° for clarity, whereas the refinement was carried out in the range 3–90°. The refinement converged to R_p = 8.02% and wR_p = 11.68%.

Figure 6

(Left and center) Crystal structure of H-ORV view along a, b without hydrogens. (Right) In the b projection, one layer of molecule chains is highlighted by orange lines. The chains are indicated by orange arrows. Color code: brown C, red O, light blue O of the water molecules.

Figure 7

(a) Interconversion equilibrium between ORV forms 1 and 2. The related thermodynamic equilibrium constant is K = 0.46. (b) The plot represents the molecular energy as a function of the dihedral angle involved in the interconversion equilibrium. ΔE = 1.94 kJ mol^–1 and E_a = 22.72 kJ mol^–1. The calculations were conducted by using a DFT theory level with a B3LYP functional and a 6-311+(3d, p) basis set.