Experimental and computational analyses of the cocrystal of tetrahydrofuran-2,3,4,5-tetracarboxylic acid and urea

• Green synthesis of novel cocrystal. • Popular acid-amide synthon along with rare synthons are analysed. • The structural studies are corroborated well with the DFT analysis. • Extensive computational studies to determine nature and strength of non-covalent interactions. In this study, a popular acid-amide supramolecular synthon is analyzed on the cocrystal of a tetracarboxylic acid with urea. A novel 1:2 cocrystal of Tetrahydrofuran-2,3,4,5-tetracarboxylic acid (also called Furan tetracarboxylic acid, FTCA) and Urea (UR) was synthesized using a neat grinding method, a green approach. The extent of proton transfer in a multi-component form to get either cocrystal or salt was predicted based on ΔpKa value, characterized by FT-IR and powder XRD analysis, and the structural confirmation by the single-XRD method. Extensive analyses of non-covalent interactions and stability of the cocrystal were done by performing different computational studies. The geometrical coordinates were optimized at B3LYP/6-311G(d,p) using density functional theory (DFT) calculations, resulting in comparable geometrical parameters of the optimized structure with the experimental data. Frontier molecular orbitals (FMOs) were obtained for kinetic/thermodynamic stability of the cocrystal, and Molecular electrostatic potential (MESP) diagrams were used to analyze various available interacting regions. The nature and strength of non-covalent interactions present in the optimized structure of cocrystal were calculated using QTAIM, NCI-RDG, and NBO analyses. Furthermore, the qualitative and quantitative estimations of weak and strong non-covalent interactions in the crystal structure were estimated by Hirshfeld surface analysis mapped over different parameters, interaction energy calculations, and total energy frameworks. :