Unsymmetrical salen-based oxido V^IV: Synthesis, characterization, biomolecular interactions, and anticancer activity

Three stable oxidovanadium(IV) [V^IVOL^1-3] complexes (1-3) were synthesized through the incorporation of unsymmetrical salen ligands (H₂L^1-3). All the ligands are synthesized, and their vanadium compounds were thoroughly characterized by CHNS analysis, various spectroscopy methods (IR, UV-Vis, NMR spectroscopy), and HR-ESI-MS. The structures of 1-3 were validated through the single-crystal X-ray analysis. UV-Vis and HR-ESI-MS were used to determine the solution stability of the complexes in the aqueous phase, revealing their stability in aqueous/biological medium. Various spectroscopy techniques were used to study the DNA/BSA binding abilities, and the results indicate that 1-3 shows effective biomolecular interactions. The partition coefficient result indicates that 1-3 are highly hydrophobic and may easily permeate the cells. Finally, the in vitro anticancer properties of 1-3 were determined with two cancerous (HT-29 and A549), and the NIH-3T3 normal cell lines. Among the series, 3 is the most cytotoxic, with IC₅₀ values of 6.2 ± 0.2 and 5.3 ± 0.4 μM against HT-29 and A549 cell lines respectively. Moreover, the apoptotic cell death mechanism of 1-3 was assessed through DAPI, AO/EB, and double staining apoptosis experiments.