Targeted Protein Interactions Driven by Hybrid Vanadium-Oxo Clusters in Solution

Metal-oxo clusters, specifically polyoxometalates (POMs), have garnered significant attention due to their potential as powerful bioinorganic catalysts capable of modulating protein functions through targeted interactions. Herein, we investigate the solution-based interactions between the hybrid vanadium-oxo cluster [V₆O₁₃{(OCH₂)₃CCH₂OH}₂]²⁻ (V₆-OH) and hen egg white lysozyme (HEWL), utilizing a combination of ⁵¹V NMR spectroscopy, cyclic voltammetry (CV), fluorescence spectroscopy, circular dichroism (CD) spectroscopy, Ultraviolet Visible (UV-vis) spectroscopy, and isothermal titration calorimetry (ITC). We confirmed a spontaneous binding of V₆-OH to HEWL with high specificity, indicated by a negative Gibbs free energy (ΔG°), substantial increase in ⁵¹V NMR signal line widths and changes in the electrochemical potential upon protein binding. Fluorescence quenching analysis revealed strong binding affinities that was further supported by ITC, while CD spectroscopy demonstrated minimal perturbation of HEWL secondary structure, indicating structural preservation upon V₆-OH binding. The strong binding affinity and the redox potential shift upon binding explain the unique ability of hybrid hexavanadates to form selective and robust interactions with proteins that facilitate localized redox activities, which are crucial for targeted biocatalytic and potential therapeutic applications.