Rational design, synthesis, computational studies and biological evaluation of new diazepanone derivatives: Crystal structure of 2,7-bis(4-chlorophenyl)-1,3-dimethyl-1,4-diazepan-5-one

• Published in: Journal of molecular structure 2025-02, Vol.1322, p.140360, Article 140360
• Main Authors: Shalo, R. Reshwen, Karthiga, A.R., Divyabharathi, S., Balasankar, T., Rajeswari, K., Vidhyasagar, T.
• Format: Article
• Language: English
• Subjects: 1,4-diazepanone; Core of liponucleoside; DFT; Energy framework and antibacterial activity; Hirshfeld surface analysis; Single crystal XRD
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.140360

•The derivatives of 2,7-bis(4-halophenyl)−1,3-dimethyl-1,4-diazepan-5-one are synthesized.•Characterized of the compounds by FT-IR, HRMS (ESI) and NMR spectral techniques.•Chair conformation of diazepanone ring conformed by single crystal XRD and NMR spectral studies.•Comparison of experimental and theoretical results.•Anti-bacterial evaluation by in vitro studies. Structural and biological evaluation of newly designed and synthesized diazepanone derivatives (3a-c) with modified functionalities is reported in this paper, as liponucleoside class of antibiotics possessing 1,4-diazepanone as core moiety are under investigation since last decade to improvise their drug action. FT-IR, HR-ESI-MS, 1H NMR and 13C NMR spectral studies are used for the structural characterization of synthesized compounds (3a-c). 1H NMR spectral data reveal that the diazepanone ring exhibits chair conformation in solution state. The solid state geometry for compound 3a acquired by SC-XRD study also in favour of chair conformation of the diazepanone ring with equatorial orientation of all the substituents. Comparison of experimental bond parameters with theoretical results attained by DFT studies using B3LYP/6–311G++ (d,p) basis set are in good agreement. Molecular electrostatic potential surface (MEPS) and HOMO-LUMO energies are used to elucidate the topology and physicochemical parameters of 3a. Nature of crystal packing is ascertained by Hirshfeld surface and its delineated 2D-Fingerprint plot in addition with the SC-XRD evidences. Antibacterial evaluation of (3a-c) against tested bacterial strains reveals that the compounds have remarkable antibacterial potencies compared to tested standard drug. Among the compounds 3a-c, the compound 3c with fluoro-substitution on the phenyl ring shows highest activity.