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

• Published in: Journal of molecular structure 2023-05, Vol.1280, p.135072, Article 135072
• Main Authors: Jyothi, K.L., Hema, M.K., Kumara, Karthik, Guru Row, T.N., Lokanath, N.K.
• Format: Article
• Language: English
• Subjects: 3D energy framework; SARS CoV-2; Stoichiometry; Supramolecular motifs; Thymine-gallic acid cocrystal
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135072

•Novel cocrystal of thymine and gallic acid was prepared and crystallized.•Initial characterization was carried out using FTIR technique.•3D molecular structure was confirmed by single-crystal X-ray diffraction method.•Intermolecular interactions and synthon formation were substantiated using HSA.•DFT analysis of TY-GA cocrystal was reported.•Most reactive sites of the novel molecule are identified.•Molecular docking study has been discussed. Physical and chemical property enhancement of an active pharmaceutical ingredient through a multicomponent 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 characterized 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–π and π…π interactions apart from the conventional hydrogen bond interactions. Furthermore, the Hirshfeld surface analysis was carried out to quantify the contribution of hydrogen bond interactions 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. [Display omitted]