Bioactive O^N^O^ Schiff base appended homoleptic titanium(iv) complexes: DFT, BSA/CT-DNA interactions, molecular docking and antitumor activity against HeLa and A549 cell lines

Abstract

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.