Thioacetamide (TAA) is used in pharmaceutical and industrial applications and has also been reported as a fungicidal agent; however, it poses serious health risks due to its hepatotoxic and immunosuppressive effects. Despite this toxicological importance, the molecular interplay of TAA with serum albumins, major plasma proteins that regulate transport, distribution, and bioavailability, remains insufficiently defined. Here, we systematically examined the binding of TAA to bovine serum albumin (BSA) under physiological conditions. UV-visible absorption, steady-state fluorescence spectroscopy (including synchronous and three-dimensional fluorescence), dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and differential pulse voltammetry (DPV) were integrated with molecular docking and molecular dynamics (MD) simulations. Fluorescence titration revealed concentration-dependent quenching with temperature dependence and moderate affinity (Ka on the order of 103-104 M-1), with approximately one dominant binding site per BSA molecule. Thermodynamic analysis indicated a spontaneous process (ΔG < 0) with predominantly hydrophobic contributions. Synchronous and 3D fluorescence measurements showed pronounced microenvironmental changes around tryptophan residues, consistent with conformational rearrangements of BSA upon TAA binding. DLS further supported complex formation by showing an increase in the hydrodynamic diameter of BSA after TAA addition. DPV measurements exhibited a gradual decrease in the TAA oxidation current in the presence of BSA.
Murathan et al. (Wed,) studied this question.