A Series of Non-Oxido V IV Complexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity.

A series of mononuclear non-oxido vanadium(IV) complexes, [V IV (L 1-4 ) 2 ] ( 1-4 ), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands H 2 L 1-4 , are reported. All the synthesized non-oxido V IV compounds are characterized by elemental analysis, spectroscopy (IR, UV-vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of 1 - 3 reveal that the mononuclear non-oxido V IV complexes show distorted octahedral ( 1 and 2 ) or trigonal prismatic ( 3 ) arrangement around the non-oxido V IV center. EPR and DFT data indicate the coexistence of mer and fac isomers in solution, and ESI-MS results suggest a partial oxidation of [V IV (L 1-4 ) 2 ] to [V V (L 1-4 ) 2 ] + and [V V O 2 (L 1-4 )] - ; therefore, all these three complexes are plausible active species. Complexes 1 - 4 interact with bovine serum albumin (BSA) with a moderate binding affinity, and docking calculations reveal non-covalent interactions with different regions of BSA, particularly with Tyr, Lys, Arg, and Thr residues. In vitro cytotoxic activity of all complexes is assayed against the HT-29 (colon cancer) and HeLa (cervical cancer) cells and compared with the NIH-3T3 (mouse embryonic fibroblast) normal cell line by MTT assay and DAPI staining. The results suggest that complexes 1 - 4 are cytotoxic in nature and induce cell death in the cancer cell lines by apoptosis and that a mixture of V IV , V V , and V V O 2 species could be responsible for the biological activity.