Mononuclear Co(III), Ni(II) and Cu(II) complexes of tridentate di‐tert‐butylphenylhydrazone: Synthesis, characterization, X‐ray crystal structures, Hirshfeld surface analysis, molecular docking and in vivo anti‐inflammatory activity

• Published in: Applied organometallic chemistry 2018-06, Vol.32 (6), p.n/a
• Main Authors: Chimmalagi, Geeta H., Kendur, Umashri, Patil, Sunil M., Gudasi, Kalagouda B., Frampton, Christopher S., Budri, Mahantesh B., Mangannavar, Chandrashekhar V., Muchchandi, Iranna S.
• Format: Article
• Language: English
• Subjects: anti‐inflammatory activity; Carrageenan; Chemical synthesis; Chemistry; Coordination compounds; Copper; Crystal structure; Hirshfeld surface analysis; Hydrazones; Hydrogen bonding; Hydroxybenzaldehydes; In vivo methods and tests; Ligands; Lipoxygenase; Molecular chains; Molecular docking; Nickel; Proteins; Surface analysis (chemical); transition metal complexes; X-ray diffraction; X‐ray diffraction study
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.4337

A new hydrazone (LH2) derived from the condensation of 2‐(4‐fluorobenzamido)benzohydrazide with 3,5‐di‐tert‐butyl‐2‐hydroxybenzaldehyde was used to synthesize Co(III), Ni(II) and Cu(II) complexes. These were characterized using various physicochemical, thermal, spectroscopic and single‐crystal X‐ray diffraction techniques. All the complexes crystallize in a monoclinic crystal system with P21/n space group and Z = 4. Structural studies of [Co(L)(LH)]⋅H2O indicate the presence of both amido and imidol tautomeric forms of the ligand, resulting in a distorted octahedral geometry around the Co(III) ion. On the other hand, in the [Ni(L)(DMF)] and [Cu(L)(H2O)] complexes, the ligand coordinates to the metal through imidol form resulting in distorted square planar geometry, in which the fourth position is occupied by the oxygen of coordinated DMF in [Ni(L)(DMF)] and by a water molecule in [Cu(L)(H2O)]. Hirshfeld surface calculations were performed to explore hydrogen bonding and C―H⋅⋅⋅π interactions. Molecular docking studies were carried out to study the interaction between the synthesized compounds and proteins (cyclooxygenase‐2 and 5‐lipoxygenase). The complexes along with the parent ligand were screened for their in vivo anti‐inflammatory activity, using the carrageenan‐induced rat paw oedema method. The complexes show significant anti‐inflammatory potencies. Mononuclear Co(III), Ni(II) and Cu(II) complexes with (E)‐N′‐(3,5‐di‐tert‐butylsalicylidene)‐2‐(4‐fluorobenzamido)benzohydrazide have been synthesized and structurally characterized using single‐crystal X‐ray diffraction studies. Intermolecular interactions were investigated using Hirshfeld surfaces. Synthesized compounds were docked with cyclooxygenase‐2 and 5‐lipoxygenase proteins and screened for in vivo anti‐inflammatory activity.