Multi-faceted investigation of copper(II) chelates based on ONS donor thiosemicarbazone: Crystal structures, spectral aspects, DNA binding, cytotoxicity and computational studies

• Published in: Journal of molecular structure 2025-01, Vol.1319, p.139463, Article 139463
• Main Authors: Jacob, Jinsa Mary, Mohan, Nithya, S．S．, Sreejith, Sithambaresan, M., Manoj, E., Kurup, M.R. Prathapachandra
• Format: Article
• Language: English
• Subjects: Copper(II) chelate; Cytotoxicity; DNA binding; FMO analysis; Hirshfeld analysis; Molecular docking; Single crystal XRD; Thiosemicarbazone
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139463

•Copper(II) chelates of a thiosemicarbazone were synthesized.•Single crystal X-ray analysis of two complexes confirms square pyramidal geometry.•DNA binding study revealed that the chelates bind to the nucleic acid in a groove-binding mode which is validated by molecular docking studies.•FMO analysis unveiled the reactivity and polarizability of the chelates.•Hirshfeld surface analysis provided insights into the intermolecular interactions of copper complexes.•In vitro cytotoxicity studies proved that copper complexes can have promising applications in biomedicine. This investigation unveils the synthesis and characterization of a binuclear copper(II) chelate [(Cubmpt)2] (1) and four heteroleptic copper(II) chelates [Cu(bmpt)(hb1)] (2), [Cu(bmpt)(hb2)] (3), [Cu(bmpt)(hb3)] (4) and [Cu(bmpt)(hb4)] (5) based on an ONS donor thiosemicarbazone ligand, 5‑bromo-3-methoxysalicylaldehyde-N4-phenylthiosemicarbazone (H2bmpt) and the heterocyclic bases 1,10-phenanthroline (hb1), 2,2′-bipyridine (hb2), 4,4′-dimethylbipyridine (hb3), 5,5′-dimethylbipyridine (hb4) as ancillary ligands. The crystal architectures of chelates 3 and 5 are ascertained using single crystal X-ray diffraction method and it is observed that they occupy triclinic P1¯ and monoclinic P21/c crystal lattice systems correspondingly. Copper(II) ion exhibits an asymmetric square pyramidal arrangement in both complexes. The DNA binding studies suggest a groove binding mechanism, with complex 4 exhibiting the highest binding value. The experimental findings on DNA binding are strongly validated by complementary in-silico investigations employing molecular docking analyses. The FMO analysis of the compounds indicates that the dimeric complex 1 possesses the highest chemical reactivity and polarizability. Hirshfeld surface analysis shed light on noncovalent interactions among complexes (3a and 5) and the results corroborate the crystal structure studies. The in vitro cytotoxicity studies involving Dalton Lymphoma Ascites (DLA) cell lines revealed that complex 5 exhibited the highest cytotoxicity. [Display omitted]