Synthesis, characterization and <i>in vitro</i> studies of metallacyclic derivatives of titanium( <scp>iv</scp> ) incorporated with Schiff's bases: DNA/BSA binding, computational aspects and cytotoxic potential

A series of four new homoleptic titanium(IV) derivatives, [TiIV(L1-4)2], were synthesized by treating titanium(IV) isopropoxide with diverse Schiff base ligands (L1-4) in 1 : 2 stoichiometry in anhydrous tetrahydrofuran. Subsequently, the complexes were extensively characterized using spectroscopic tools: FTIR spectroscopy, UV-Vis spectroscopy, ¹H, ¹³C NMR and HRMS. Molecular structures of the complexes [TiIV(L1,3)2] were analyzed crystallographically, which appeared as monoclinic with the <i>C</i>₁2/<i>c</i>₁ space group for [TiIV(L1)2], while [TiIV(L3)2] adopted a tetragonal pattern possessing the space group <i>P</i>4₁2₁2. The electronic structures of the complexes were studied to understand their properties during different sorts of interactions employing various computational techniques, such as density functional theory (DFT), molecular docking and Hirshfeld surface analysis (HSA). Further, the optimized molecular structures were derived from B3LYP/6-311G (d,p) Gaussian (09) software. HSA was used to the intermolecular interactions of the crystal system and the contribution of individual elements to the 3D architecture. UV-Visible absorption and fluorescence techniques were employed to assess the binding interactions of BSA and CT-DNA individually with these newly synthesized titanium(IV) derivatives. The drug-likeness of the titanium(IV) derivatives was validated through ADMET investigations. <i>In vitro</i> studies of the complexes [TiIV(L1-4)2] were carried out against HT-29 and MCF-7 cell lines. Among these newly synthesized complexes, [TiIV(L2)2] was found to be the most cytotoxic with IC₅₀ values of 27.25 μg mL^-1 and 37.72 μg mL^-1 against HT-29 cells and MCF-7 cells, respectively.