Bioactive O^N^O^ Schiff base appended homoleptic titanium(iv) complexes: DFT, BSA/CT-DNA interactions, molecular...

Five new homoleptic derivatives of titanium(iv) have been developed and characterized by physicochemical techniques. Metal complexes, TiH₂L¹ [(C₃₈H₂₆N₆O₄)Ti], TiH₂L² [(C₃₈H₂₄F₂N₆O₄)Ti], TiH₂L³ [(C₃₈H₂₄Cl₂N₆O₄)Ti], TiH₂L⁴ [(C₃₈H₂₄Br₂N₆O₄)Ti] and TiH₂L⁵ [(C₃₈H₂₄N₈O₈)Ti], were obtained by treating Ti(OPrⁱ)₄ with appropriate ONO ligands (H₂L¹-H₂L⁵) in anhydrous THF as solvent. The electronic structures and properties of titanium(iv) complexes (TiH₂L¹-TiH₂L⁵) and ligands (H₂L¹-H₂L⁵) were examined by DFT studies. The stability of all synthesized derivatives was assessed by a UV-visible technique using 10% DMSO, GSH medium and n-octanol/water systems. The binding interactions of BSA and CT-DNA with respective titanium(iv) complexes were successfully evaluated by employing UV-visible absorption, fluorescence, circular dichroism (CD) techniques and docking studies. The in vitro cytotoxicity of TiH₂L², TiH₂L³ and TiH₂L⁴ complexes was assessed against HeLa (human epithelioid cervical cancer cells) and A549 (lung carcinoma) cell lines. The IC₅₀ values of TiH₂L², TiH₂L³ and TiH₂L⁴ were observed to be 28.8, 14.7 and 31.2 μg mL^-1 for the HeLa cell line and 38.2, 32.9 and 67.78 μg mL^-1 for A549 cells, respectively. Complex TiH₂L³ exhibited remarkably induced cell cycle arrest in the G₁ phase and 77.99% ROS production selectivity in the HeLa cell line.