Binding of Aqueous-Stable, Lipophilic, Hemocompatible Anticancer V ^V O ₂ Metallodrugs with Biological Molecules: X-ray Structures of the Adduct of the V ^V –hydrazonato Complex with Hen Egg White Lysozyme

Three new water-stable aqueous dioxidovanadium(V) complexes, [(V^VO₂L^1-3)M(H₂O)_n] (<b>1</b>-<b>3</b>), 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 <b>1</b>-<b>3</b> were investigated using conventional techniques. High-resolution molecular structures of the adduct formed between <b>1</b> 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 <b>1</b> to HEWL was also evaluated through different spectroscopic methods. Fluorescence data indicate that <b>1</b> can also bind the physiologically relevant protein human serum albumin at pH 7.4. Furthermore, the cytotoxicity of <b>1</b>-<b>3</b> 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. <b>1</b> (IC₅₀ value of 9.2 ± 0.1 μM) is more effective than the other two complexes. It induces cell death via apoptosis.