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Updated: Oct 1, 2025

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example
Published on: November 18, 2015
A new bioactive cocrystal of coumarin-3-carboxylic acid and thiourea: detailed structural features and biological
Muhammad Shahbaz1, Umair Ahmed Khan1, M Iqbal Chaudhary1
1H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Sindh 75270, Pakistan.
Abstract:
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, C10H6O4), a synthetic analogue of the naturally occurring antioxidant coumarin, with thiourea (CH4N2S) 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 (-NH2) groups of thiourea and the carbonyl group of coumarin. The synthesized cocrystal exhibited potent antioxidant activity (IC50 = 127.9 ± 5.95 µM) in a DPPH radical scavenger assay in vitro in comparison with the standard N-acetyl-L-cysteine (IC50 = 111.6 ± 2.4 µM). The promising results of the present study highlight the significance of cocrystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients.
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