Homoleptic complexes of titanium(iv) fused with O^N^O Schiff base derivatives: design, BSA–DNA interaction, molecular docking, DFT and cytotoxicity†

A set of six Ti(IV) complexes (Ti-1-IS, Ti-2-IN, Ti-3-IO, Ti-4-IF, Ti-5-ICl and Ti-6-IBr) associated with (Z)-N-((E)-2-hydroxybenzylidene) isonicotinohydrazonic acid derivatives were developed while treating titanium(IV) isopropoxide with the appropriate ligands in a stoichiometry of 1 : 2 using anhydrous tetrahydrofuran (THF). Later, the purified products were characterized by employing the spectral techniques FTIR, UV-vis, NMR and HRMS. Then, these newly established complexes were subjected to biomedical applications such as DNA–BSA interaction and in vitro cytotoxic investigations. Afterwards, the DNA/BSA binding results of these six complexes revealed that complexes Ti-4-IF and Ti-5-ICl displayed greater binding constant values with DNA and BSA of 2.97 × 10⁵ M⁻¹ and 0.065 × 10⁴ M⁻¹, respectively. Ethidium bromide (EtBr) was competitively displaced from DNA by the groove-binding mechanism on employing titanium(IV) complexes, and this observation was well supported by viscosity, cyclic voltammetry and in silico investigations. Electronic characteristics and molecular representation of Ti(IV) complexes were ascertained using the DFT technique. Subsequently, to explore the anticancer potential of these titanium complexes, an MTT assay was executed against non-cancerous HEK (human embryonic kidney), HeLa (cervical carcinoma) and MCF7 (breast adenocarcinoma) cells, wherein Ti-3-IO (27.17 μM) and Ti-5-ICl (24.25 μM) exhibited low IC₅₀ values, to emerge as noteworthy cytotoxic agents against the latter two cancer cell lines. Interestingly, the viability of the HeLa cell line was found to have decreased significantly by the pronounced activity of these complexes. Further, acridine orange–ethidium bromide (AO–EB) staining, cell cycle analysis by propidium iodide (PI) staining and determination of reactive oxygen species (ROS) were also carried out to determine the potency and credibility of titanium(IV) derivatives.