Synthesis and Characterization of a (−)-Epicatechin and Barbituric Acid Cocrystal: Single-Crystal X‑ray Diffraction and Vibrational Spectroscopic Studies

The paper presents the contribution of the cocrystallization method in the physicochemical modification of catechins that exhibit low oral bioavailability. This was done to obtain cocrystals for two naturally occurring polyphenolic diastereoisomers (+)-catechin and (−)-epicatechin with commonly used coformers. Due to distinct crystallization behavior, only the (−)-epicatechin cocrystal with barbituric acid in a 1:1 stoichiometry was obtained. The cocrystal of (−)-epicatechin (EC) with barbituric acid (BTA) was prepared by the slow solvent-evaporation technique. The structure and intermolecular interactions were determined by X-ray crystallographic techniques. The analysis of packing and interactions in the crystal lattice revealed that molecules in the target cocrystal were packed into tapes, formed by the O–H···O type contacts between the (−)-epicatechin and coformer molecules. The EC molecules interact with the carboxyl group in the BTA coformer mainly by −OH groups from the benzene ring A. The cocrystalline phase constituents were also investigated in terms of Hirshfeld surfaces. The application of Raman spectroscopy confirmed the involvement of the CO group in the formation of hydrogen bonds between the (−)-epicatechin and barbituric acid molecules. Additionally, the solubility studies of pure EC and the EC-BTA cocrystal exhibited minor enhancement of EC solubility in the buffer solution, and pH measurements confirmed a stable level of solubility for EC and its cocrystal.