A new bioactive cocrystal of coumarin-3-carboxylic acid and thiourea: detailed structural features and biological activity studies

Cocrystallization is a phenomenon widely used to enhance the biological and physicochemical properties of active pharmaceutical ingredients (APIs). The present study deals with the synthesis of a cocrystal of coumarin-3-carboxylic acid (2-oxochromene-3-carboxylic acid, C 10 H 6 O 4 ), a synthetic analogue of the naturally occurring antioxidant coumarin, with thiourea (CH 4 N 2 S) using the neat grinding method. The purity and homogeneity of the coumarin-3-carboxylic acid–thiourea (1/1) cocrystal was confirmed by single-crystal X-ray diffraction, FT–IR analysis and thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed geometry analysis via density functional theory (DFT) demonstrated that the 1:1 cocrystal stoichiometry is sustained by N—H...O hydrogen bonding between the amine (–NH 2 ) groups of thiourea and the carbonyl group of coumarin. The synthesized cocrystal exhibited potent antioxidant activity (IC 50 = 127.9 ± 5.95 µ M ) in a DPPH radical scavenger assay in vitro in comparison with the standard N -acetyl-L-cysteine (IC 50 = 111.6 ± 2.4 µ M ). The promising results of the present study highlight the significance of cocrystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients.