Comparison of the crystal structures and physicochemical properties of novel resveratrol cocrystals

Abstract

Resveratrol (RSV) is one of the most extensively investigated natural polyphenol with potential cardioprotective effects and various biological activities. However, the polymorphism and solvates of RSV cocrystals have not been studied comprehensively. In addition, the relationship between the crystal packing modes and their physicochemical properties of RSV cocrystals remains poorly understood. In this paper, seven novel RSV cocrystals were prepared and characterized by powder X-ray diffraction, single-crystal X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, dynamic vapor sorption, Raman and Fourier transform infrared spectroscopy. Five RSV–4,4′-vinylenedipyridine (DPE) cocrystals were synthesized with polymorphs and solvates, such as RSV–DPE (1:2) in form (I) [RSV–2DPE form (I)], RSV–DPE (1:2) in form (II) [RSV–2DPE form (II)], RSV–DPE (1:1) (RSV–DPE), RSV–DPE (2:3)·acetone (RSV–1.5DPE·0.5ACE), RSV–DPE (1:1.5)·MeOH (RSV–1.5DPE·MeOH). However, RSV–4,4′-ethylenedipyridine (BPE) and RSV–4,4′-azobispyridine (AZPY) cocrystals were prepared as their single crystal forms, that is, RSV–BPE (1:1.5) (RSV–1.5BPE) and RSV–AZPY (1:2) (RSV–2AZPY). RSV–2DPE form (II) can be transformed from RSV–2DPE form (I) during the heating process from single crystal to single crystal. The physicochemical properties of RSV cocrystals are closely related to their crystal packing modes. Also, the conformation and molecular packing of RSV among different cocrystals is flexible. The solubility of RSV–1.5BPE and RSV–2DPE form (II) exhibit higher than RSV in the buffer solution of pH 4.6 and 2.0, respectively. This study may provide a valuable insight into the crystal packing modes of cocrystals which may affect their physicochemical properties.