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

[Image: see text] 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.