Structure-property relationship of two gamma-lactam derivatives: Hirshfeld surface analysis, DFT, and molecular dynamics simulations

• Published in: Chemical physics letters 2024-12, Vol.857, p.141725, Article 141725
• Main Authors: Xue, Fan, Preetham, Habbanakuppe D, Verma, Rameshwari, Chandra, Lohith, T.N., Raju, Sahana, S., Divakara, Sajid Ali, Mohd, Al-Lohedan, Hamad A., Ramakrishna, Harsha, Sharath Kumar, Kothanahally S., Hamse Kameshwar, Vivek
• Format: Article
• Language: English
• Subjects: DFT; Gamma-lactam; Hirshfeld surface analysis; Molecular docking
• ISSN: 0009-2614
• DOI: 10.1016/j.cplett.2024.141725

[Display omitted] •Structures of compound 2a and 2b is examined by single crystal X-ray diffraction.•Fingerprint plot recognize the major contribution of H….H contacts.•HOMO-LUMO and MEP analyses explored the physicochemical properties.•Drug-Likeness properties and ADME analysis was conducted. Complete structural and non-covalent interactions of 2a and 2b are examined by single crystal X-ray diffraction and computational studies. Hirshfeld surface analysis showed differences in the relative contribution of non-covalent interactions of 2a and 2b. Fingerprint plots recognize the major contribution of H…H contacts in 2a and 2b. Density functional theory using implicit solvation models, the energy gap of the frontier molecular orbitals found to be 4.624 eV in 2a and 4.264 eV in 2b. Docking studies predicted that 2a and 2b have suitable structures to target Human Topoisomerase II Alpha, which was further validated using MM/GBSA and MDSs studies.