Structural elucidation of 1:4:4 stochiometric form of thymine-gallic acid cocrystal hydrate: Hirshfeld surface analysis, 3D energy framework, DFT calculations, and SARS CoV-2 docking studies

Physical and chemical property enhancement of an active pharmaceutical ingredient through a multi -component form is an integral part of the pharmaceutical research. A novel binary compound of thymine (TY) with gallic acid (GA) has been obtained by a solid-state grinding process and preliminarily charac-terized by FTIR technique. The single crystals were obtained and the 3D molecular crystal structure was confirmed by X-ray diffraction studies. The novel binary compound was crystallized as a cocrystal hydrate [TY-GA-H2O] in the monoclinic P21/c space group with an 1:4:4 stoichiometry. Crystal structure analysis revealed the presence of both intra and intermolecular hydrogen bond interactions, which resulted in the formation of various supramolecular architectures. Further, the structural analysis explored the presence of lone pair- & pi; and & pi;...& pi; interactions apart from the conventional hydrogen bond interactions. Further-more, the Hirshfeld surface analysis was carried out to quantify the contribution of hydrogen bond in-teractions in stabilizing the crystal structure. The individual interaction energies and the total interaction energy between the molecules were computed through energy framework analysis. HOMO-LUMO plots and MEP surface were generated to understand the electronic structure and chemical reactive sites of the molecule respectively. Finally, the molecular docking analysis was carried out to examine the antiviral properties of the novel TY-GA cocrystal hydrate. & COPY; 2023 Elsevier B.V. All rights reserved.