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, TiH ₂L ¹ [(C ₃₈H ₂₆N ₆O ₄)Ti], TiH ₂L ² [(C ₃₈H ₂₄F ₂N ₆O ₄)Ti], TiH ₂L ³ [(C ₃₈H ₂₄Cl ₂N ₆O ₄)Ti], TiH ₂L ⁴ [(C ₃₈H ₂₄Br ₂N ₆O ₄)Ti] and TiH ₂L ⁵ [(C ₃₈H ₂₄N ₈O ₈)Ti], were obtained by treating Ti(OPr ⁱ) ₄ with appropriate ONO ligands (H ₂L ¹–H ₂L ⁵) in anhydrous THF as solvent. The electronic structures and properties of titanium( iv) complexes (TiH ₂L ¹–TiH ₂L ⁵) and ligands (H ₂L ¹–H ₂L ⁵) 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 TiH ₂L ², TiH ₂L ³ and TiH ₂L ⁴ complexes was assessed against HeLa (human epithelioid cervical cancer cells) and A549 (lung carcinoma) cell lines. The IC ₅₀ values of TiH ₂L ², TiH ₂L ³ and TiH ₂L ⁴ 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 TiH ₂L ³ exhibited remarkably induced cell cycle arrest in the G ₁ phase and 77.99% ROS production selectivity in the HeLa cell line.

Abstract

Five new homoleptic derivatives of titanium( iv) have been developed and characterized by physicochemical techniques.