Binding of Aqueous-Stable, Lipophilic, Hemocompatible Anticancer VVO2 Metallodrugs with Biological Molecules: X-ray Structures of the Adduct of the VV-hydrazonato Complex with Hen Egg White Lysozyme.

Three new water-stable aqueous dioxidovanadium(V) complexes, [(VVO2L1-3)M(H2O)n] (1-3), incorporating hydrazone ligands with different alkali metals (Na+/K+) as counterions were synthesized and characterized by various physicochemical approaches, including single-crystal X-ray diffraction (SCXRD). Time-dependent spectroscopic/spectrometric techniques were used to determine their aqueous-phase stabilities. Blood compatibility studies were employed to investigate their efficacy and stability with human red blood cells. Lipophilicity and calf thymus (CT)-DNA interaction of 1-3 were investigated using conventional techniques. High-resolution molecular structures of the adduct formed between 1 and hen egg white lysozyme (HEWL) were determined by SCXRD. The structural analysis reveals that the compound self-assembles within protein crystals, forming a dimeric structure that non-covalently interacts with the protein surface. The binding of 1 to HEWL was also evaluated through different spectroscopic methods. Fluorescence data indicate that 1 can also bind the physiologically relevant protein human serum albumin at pH 7.4. Furthermore, the cytotoxicity of 1-3 was evaluated against the lung (A549) and human breast adenocarcinoma (MCF-7) cancer cell lines, as well as an human embryonic kidney cell line (HEK-293) noncancerous cell line. 1 (IC50 value of 9.2 ± 0.1 μM) is more effective than the other two complexes. It induces cell death via apoptosis.