Electrochemical sensing of organoferrocene ligand interaction with serum albumin in dimethyl sulfoxide media.

Protein-ligand interactions are crucial for understanding biochemical reactions and pathways, as well as for the design of new therapeutics. In this work, we compare the electrochemical behavior of four neutral organoferrocene ligands that differ in the number of monosaccharide and ferrocene units. The presence of a carbohydrate moiety results in increased hydrophilicity, while ferrocene units increase hydrophobicity, which significantly influences interactions with the surface, as well as with serum albumin. The adsorption of di-ferrocene ligands on the electrode surface and to serum albumin is more pronounced than that of mono-ferrocenes. Additionally, di-ferrocene ligands require dissolution in organic solvents, such as dimethyl sulfoxide, which also influences ligand-electrode and ligand-protein affinities. The conclusions of our work highlight the importance of ligand nature in determining the dissociation constant and mutual interactions with proteins, including those where ligands bind non-specifically. Electrochemical methods are suitable for studying the interactions of hydrophobic ligands with proteins because the ligands are typically present at micromolar concentrations to ensure their solubility in water. In addition, these methods exhibit high sensitivity to subtle structural changes of the protein.