New mixed ligand oxidovanadium(IV) complexes: Solution behavior, protein interaction and cytotoxicity

• Published in: Journal of inorganic biochemistry 2022-08, Vol.233, p.111853-111853, Article 111853
• Main Authors: Lima, Sudhir, Banerjee, Atanu, Sahu, Gurunath, Patra, Sushree Aradhana, Sahu, Kausik, Sasamori, Takahiro, Sciortino, Giuseppe, Garribba, Eugenio, Dinda, Rupam
• Format: Article
• Language: English
• Subjects: Aroylhydrazone; Cytotoxicity; DFT study; Oxidovanadium(IV); Protein interaction; X-ray crystal structure
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2022.111853

Herein we report the synthesis of five new mononuclear mixed ligand oxidovanadium(IV) complexes [VIVO(L1−3)(LNN)] (1–5) with tridentate O,N,O-donor aroylhydrazones as main ligand (H2L1–3) and N,N-chelating 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen) as co-ligand (LNN). The complexes were characterized by elemental and thermogravimetric analysis (TGA), IR, UV–vis, and electron paramagnetic resonance (EPR) spectroscopy, electrospray ionization-mass spectrometry (ESI–MS) and cyclic voltammetry (CV). The structure of 1–5 was confirmed by single crystal X-ray analysis and also optimized by density functional theory (DFT) methods. At physiological pH an equilibrium [VIVO(L1–3)(LNN)] + H2O ⇄ [VIVO(L1–3)(H2O)] + LNN, shifted towards left, is established, with water molecule that could be replaced by the biomolecules of the organism. The studies on the interaction with two proteins, lysozyme (Lyz) chosen as a representative model of a small protein, and human serum albumin (HSA) show that two types of binding are possible: a non-covalent binding through the accessible residues on protein surface with [VIVO(L1–3)(LNN)] keeping its octahedral structure, and a covalent binding upon the replacement of water in [VIVO(L1–3)(H2O)] with His-N donors to form VIVO(L1–3)(HSA). In vitro cytotoxicity of ligands and complexes were screened against human cervical cancer (HeLa) (IC50 = 7.39–15.13 μM), colon cancer (HT-29) (IC50 = 11.04–28.20 μM) and mouse embryonic fibroblast (NIH-3T3) cell lines (IC50 = 62.22–87.75 μM) by MTT assay. Particularly, 5 showed higher cytotoxicity than cisplatin and cyclophosphamide, with an IC50 of 7.39 ± 1.21 μM and 11.04 ± 0.29 μM against HeLa and HT-29. New mixed ligand oxidovanadium(IV) complexes [VIVO(L1–3)(bipy/phen)] incorporating three aroylhydrazones (H2L1–3) as the main ligands and 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) as the co-ligands were synthesized and characterized. Their behavior in solution, interaction with proteins and cytotoxicity were also determined. [Display omitted] •New mixed VIVO complexes with hydrazones and bipyridine/phenanthroline were synthesized.•The five complexes (1–5) were characterized by an instrumental/computational approach.•The behavior of 1–5 in aqueous solution at physiological pH was studied.•The interaction of 1–5 with lysozyme and human serum albumin was examined.•The cytotoxicity of 1–5 on human cervical and colon cancer cell lines was evaluated.